tag:theconversation.com,2011:/id/topics/cancer-research-5785/articlesCancer research – The Conversation2023-06-08T15:16:05Ztag:theconversation.com,2011:article/2071712023-06-08T15:16:05Z2023-06-08T15:16:05ZBeauty procedures from manicures to cosmetic surgery carry risk — and the reward of a better life — podcast<figure><img src="https://images.theconversation.com/files/530387/original/file-20230606-27-d4x6su.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C3997&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">UV lights in nail salons may be associated with the risk of skin cancer.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Making yourself more beautiful can result in tangible, material rewards. <a href="https://thewalrus.ca/pretty-privilege-at-work/">Pretty privilege</a>, as it is called, can lead to greater access to money and social capital, resulting in a better quality of life.</p>
<p>In Brazil, this understanding that beauty is important to one’s social status and mental and emotional well-being has prompted the state to subsidize cosmetic surgery. But this pursuit of beauty has a dark side and can often mean exposure to harm. </p>
<p>And this isn’t limited to extreme beautification practices, like extensive cosmetic surgery. People are also willing to endure potential risks in more mundane and everyday beauty treatments — like manicures.</p>
<p>In this episode of <em>The Conversation Weekly</em>, we speak to an anthropologist and a cancer researcher about the potential harm inherent in seeking beauty treatments.</p>
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<h2>The illusion of choice</h2>
<p>Carmen Alvaro Jarrín is an associate professor of anthropology at the College of the Holy Cross in Worcester, in the U.S. They research cosmetic surgery in Brazil and looked at how the state came to support access to cosmetic procedures as part of the delivery of health care. The plastic surgeon Ivo Pitanguy had campaigned for access to cosmetic surgery, arguing that everyone had the right to be beautiful.</p>
<p>“It surprised me how many of them get plastic surgery, and spend a lot of money on beauty because they see it as a way to attain upward mobility,” Jarrín said. Their book, <a href="https://www.ucpress.edu/book/9780520293885/the-biopolitics-of-beauty"><em>The Biopolitics of Beauty: Cosmetic Citizenship and Affective Capital in Brazil</em></a>, examined how beauty became a health right. </p>
<p>Many of those who access state-subsidized clinics cannot afford cosmetic procedures privately. And these clinics come with a risk — often they are used as training centres and many patients have experimental procedures tested on them, sometimes with drastic effects.</p>
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<a href="https://theconversation.com/in-brazil-patients-risk-everything-for-the-right-to-beauty-94159">In Brazil, patients risk everything for the 'right to beauty'</a>
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<p>“People believe that beauty gives you wealth. If you’re born poor and you’re beautiful, people think that it will give you upward mobility. Everybody was convinced that they would gain upper mobility,” Jarrín explains. “Anthropologists have noticed that the more unequal a society is, and the less upward mobility there is, the more that people will take to these magical means. In Brazil, beauty has that kind of magical quality to it.”</p>
<p>Access to cosmetic surgery promises better job opportunities and social mobility. In that context, seeking medical intervention to become more beautiful can be a rational choice.</p>
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<figcaption><span class="caption">‘Unreported World’ looks at access to cosmetic surgery for lower income women in Brazil.</span></figcaption>
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<h2>The risk of exposure</h2>
<p>It’s not just plastic surgery, or in Brazil, where the pursuit of beauty can carry an extreme price. The growing popularity of gel manicures, with their employ of UV lights, can also place people at risk.</p>
<p>In 2016, Karolina Jasko — the 2018 Miss Illinois — was diagnosed with a rare form of melanoma on her thumb nail. Her cancer had been triggered by exposure to UV lights in nail parlours from getting regular manicures.</p>
<p>Maria Zhivagui is a postdoctoral researcher in environmental toxicology and cancer genomics at the University of California, in the U.S. She recently co-authored a study on <a href="https://doi.org/10.1038/s41467-023-35876-8">the impacts of using UV light to cure nail polish</a>.</p>
<p>“We started hearing about a lot of cancer cases that developed from artificial UV lamp exposure,” Zhivagui said. “We found this UV nail machine that is used in nail salons and that has been linked to cancer in females, that occurs on the dorsum of the hand or on the nail and the finger. And that was a very rare cancer, we usually don’t observe it.”</p>
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<p>Her team found that UV nail lamps can cause mutations in human and mice cells. Once she saw the effects, Zhivagui — who would often get manicures and would even do them herself at home — stopped using the UV lights.</p>
<p>“After seeing the effects on the mitochondria, on the DNA and cell death, I was like, no, this is very alarming,” she said. “And I stopped immediately getting exposed to these UV radiations in nail salons.”</p>
<p>While UV lights are widely used in nail salons, the devices are easy to acquire for home use. And as they become more widely accessible, it’s likely more people are exposing themselves to risk.</p>
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<p>This episode was written and produced by Nehal El-Hadi and Mend Mariwany, who is also the executive producer of The Conversation Weekly. Eloise Stevens does our sound design, and our theme music is by Neeta Sarl.</p>
<p>You can find us on Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a>, on Instagram at <a href="https://www.instagram.com/theconversationdotcom/">theconversationdotcom</a> or <a href="mailto:podcast@theconversation.com">via email</a>. You can also subscribe to The Conversation’s <a href="https://theconversation.com/newsletter">free daily email here</a>. </p>
<p>Listen to <em>The Conversation Weekly</em> via any of the apps listed above, download it directly via our <a href="https://feeds.acast.com/public/shows/60087127b9687759d637bade">RSS feed</a> or find out <a href="https://theconversation.com/how-to-listen-to-the-conversations-podcasts-154131">how else to listen here</a>.</p><img src="https://counter.theconversation.com/content/207171/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Carmen Alvaro Jarrín received a Wenner-Gren Foundation Dissertation Fieldwork Grant and Mellon/ACLS Dissertation Completion funding.</span></em></p><p class="fine-print"><em><span>Maria Zhivagui does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Being beautiful can improve a person’s quality of life and emotional wellbeing. But sometimes, there is a risk of harm — from exposure to cancer-causing UV light, to cheap cosmetic procedures.Nehal El-Hadi, Science + Technology Editor & Co-Host of The Conversation Weekly Podcast, The ConversationDaniel Merino, Associate Science Editor & Co-Host of The Conversation Weekly Podcast, The ConversationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2014072023-06-01T14:15:52Z2023-06-01T14:15:52ZBillions spent on cancer research globally – but is it money well spent?<p>In 2020, <a href="https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21660">19 million people</a> around the world received a cancer diagnosis. By 2040, that number is expected to reach 28 million. Poorer countries will be especially hard hit, with an increasing number of cases and more <a href="https://pubmed.ncbi.nlm.nih.gov/33069326/">deaths</a>, compared with richer countries.</p>
<p>Cancer research is vital to helping ease this global burden, but where and how research money is spent doesn’t always match with where and how help is needed. To get a clearer picture of where <a href="https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00182-1/fulltext">cancer research funding is spent</a>, we collected and compiled data covering public and charitable cancer research investments, globally, between 2016 and 2020, inclusive. This amounted to US$24.5 billion (£19.7 billion) of investment across 66,388 research grants.</p>
<p>By country, the US provided 57.3% of the total cancer research funding awarded, with the US National Institute of Health being by far the biggest funder. Most of the world’s biggest funders are <a href="https://health-policy-systems.biomedcentral.com/articles/10.1186/s12961-015-0074-z">transparent</a> about their funding decisions, <a href="https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30357-0/fulltext">providing</a> data on their grants. This allows for scrutiny around their portfolios and allows those who set funding priorities to better understand <a href="https://pubmed.ncbi.nlm.nih.gov/24119660/">how to allocate</a> limited resources for health research. </p>
<p>Among the major global health funders, Cancer Research UK is one of the few that does not provide data on funding at the individual award level. They rely on top-level summaries in <a href="https://www.cancerresearchuk.org/health-professional/our-reports-and-publications">annual reports</a> and other infographics, which is <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31427-1/fulltext?rss%3Dyes">insufficient</a> for analyses such as ours. This makes it difficult to look into how the money was spent in detail. </p>
<h2>Lung and thyroid cancers least funded</h2>
<p><a href="https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00182-1/fulltext">Our analysis</a> compares the level of funding given to researching different types of cancers with the health burden of those types of cancer. This is important as it allows us to understand who is funding what in cancer research and to understand whether research gaps may exist.</p>
<p>We found that the cancer types receiving the most funding were breast (US$2.73 billion, 11.2% of the total) and haematological cancer (typically referring to leukaemia, US$2.3 billion, 9.4%).</p>
<p>In terms of the type of research, preclinical research (typically laboratory studies) received US$18 billion (73.5%). Pre-clinical studies are the earliest stage of research. The hope is that the findings from this stage of research will eventually “translate” into new or better treatments for cancer. </p>
<p>Preclinical studies are followed by testing in humans – clinical trials – which can take many years. If a drug or other treatment is proven to work, it then has to be approved by the drugs regulators, such as the US Food and Drug Administration or the European Medicines Agency. </p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241518/">time taken</a> from exploring preclinical science to a treatment used in practice can be up to 17 years. Most new products fail between the preclinical or clinical trial phases – <a href="https://www.nature.com/articles/nrd.2016.136">more so</a> in oncology (the study and diagnosis of tumours) than other areas of medicine. </p>
<p>Immuno-oncology is a relatively new <a href="https://www.cancercare.org/publications/285-understanding_the_role_of_immuno-oncology_in_treating_cancer">therapeutic area</a> that tries to develop treatments to enhance the body’s immune system to fight cancer. In our analyses, immuno-oncology received 12% of the funding, reflecting the global desire to find new approaches to cancer treatments. However, such are the inequities in global health, that even if immuno-oncology and other new medicines make it into clinical practice, this will usually be in the richer countries. Poorer populations are <a href="https://theconversation.com/cancer-groundshot-access-to-proven-treatments-must-parallel-development-of-new-therapies-182400">unlikely</a> to have access to the latest treatments.</p>
<p>We then looked at what investment 18 different types of cancer received and compared this against the number of deaths caused annually by each type of cancer. Our results suggest that lung cancer was particularly poorly funded. </p>
<p>We also reviewed a measure called “years lived with disability”, which <a href="https://www.healthsystemtracker.org/indicator/health-well-being/years-lived-with-disability/">considers</a> the effect of that disease on quality of life. Here, thyroid cancer came out as least-well funded. Both lung and thyroid cancers were judged to be the least well-funded cancer conditions overall, compared to their global burdens.</p>
<h2>Cancer funding fell 45%</h2>
<p>Our results show an average annual spend over the years 2016-19 of US$5.5 billion per year, with a 45% drop to US$2.9 billion in 2020. This might have been a natural fluctuation – cancer funding levels were declining to some extent – but it’s possible the drop was caused by a diversion of funds into COVID research.</p>
<p>It’s also likely that these drops in funding will mean less new knowledge coming through the cancer research pipeline. This will further affect patients at a time when the global burden is likely to increase, and may also drive further inequalities around access to cancer treatment and care. </p>
<p>Only 0.5% of cancer funding had a primary focus on lower-income countries, so it will not be easy for populations in poorer countries to benefit from new research findings. There was <a href="https://www.gavi.org/vaccineswork/stark-reality-how-covid-19-has-worsened-global-inequality?gclid=CjwKCAjw_MqgBhAGEiwAnYOAetWVUXwDjJwvI72QhSramnBpfmSgOST7WYj7se21Y8CwSlBhl2U9rRoCzewQAvD_BwE">significant inequity</a> in the COVID response, for example, with the distribution of vaccines during the height of the pandemic. There will be continuing consequences for wellbeing in other areas of health, with the worsening burden of cancer estimated to cause <a href="https://www.bmj.com/content/376/bmj.o375">a drop</a> in life expectancy.</p>
<p>From previous experience, it’s fair to suggest that much of the preclinical research funded – by far the largest component of the portfolio – might not make it as far as being used in clinical care, and therefore only a small proportion of the current cancer research portfolio is going to be of direct benefit to patients at any point soon.</p>
<p>While some of this funding is, of course, essential for developing new treatments, the sheer volume of funding in this area means the overall portfolio may not be money well spent. While some of this type of research spending has driven innovative areas of medicine (such as immuno-oncology), there should be a new focus on prevention and also patient-focused research (such as the psychological and social effects of cancer).</p>
<p>There will be long-term consequences of the pandemic on other areas of health, including cancer. Our analysis showed the flow of funding into cancer research. This can help the global cancer research community better set future priorities. We must invest our limited global research resources as wisely as possible.</p><img src="https://counter.theconversation.com/content/201407/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Head has previously received funding from the Bill & Melinda Gates Foundation and the UK Department for International Development.</span></em></p><p class="fine-print"><em><span>Ramsey Cutress receives grant funding from the NIHR, Prevent breast cancer, World Cancer Research Fund, Association of Breast Surgery, Astra Zeneca and institutional research support from seca.</span></em></p><p class="fine-print"><em><span>Stuart McIntosh receives grant funding from the National Insititute of Health Research and Cancer Research UK. He has received institutional payments for advisory boards and speaker bureaux from MSD, Lilly, Roche, Astra Zeneca and BD Medical, and travel and conference support from Roche, MSD and Lilly.</span></em></p>Lung and thyroid cancers are the least well-funded cancers compared to their global burdens.Michael Head, Senior Research Fellow in Global Health, University of SouthamptonRamsey Cutress, Professor, Breast Surgery, University of SouthamptonStuart McIntosh, Clinical Reader in Surgical Oncology, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1982202023-02-22T12:54:26Z2023-02-22T12:54:26ZPeople produce endocannabinoids – similar to compounds found in marijuana – that are critical to many bodily functions<figure><img src="https://images.theconversation.com/files/510907/original/file-20230217-380-5ni8j3.jpg?ixlib=rb-1.1.0&rect=30%2C38%2C5077%2C3339&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A healthy endocannabinoid system is critical to the human body’s immune functions.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/older-hispanic-woman-lifting-weights-in-living-room-royalty-free-image/546825853?phrase=energy%20exercise&adppopup=true">Jose Luis Pelaez Inc/Digital Vision via Getty Images</a></span></figcaption></figure><p>Over the past two decades, a great deal of attention has been given to marijuana – also known as pot or weed. As of early 2023, marijuana has been <a href="https://www.usnews.com/news/best-states/articles/where-is-marijuana-legal-a-guide-to-marijuana-legalization">legalized for recreational use in 21 states</a> and Washington, D.C., and the use of <a href="https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/medical-marijuana/art-20137855">marijuana for medical purposes</a> has grown significantly during the <a href="https://nap.nationalacademies.org/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the-current-state">last 20 or so years</a>. </p>
<p>But few people know that the human body naturally produces chemicals that are very similar to delta-9-tetrahydrocannabinol, or THC, the psychoactive compound in marijuana, which comes from the <a href="https://doi.org/10.3389/fpls.2016.00019"><em>Cannabis sativa</em> plant</a>. These substances are called endocannabinoids, and they’re <a href="https://doi.org/10.3390%2Fani9090686">found across all vertebrate species</a>. </p>
<p>Evolutionarily, the appearance of endocannabinoids in vertebrate animals predates that of <em>Cannabis sativa</em> by <a href="https://doi.org/10.1300/J175v02n01_04">about 575 million years</a>. </p>
<p>It is as if the human body has its own version of a marijuana seedling inside, constantly producing small amounts of endocannabinoids.</p>
<p>The similarity of endocannabinoids to THC, and their importance in maintaining human health, have raised significant interest among scientists to further study their role in health and disease, and potentially use them as therapeutic targets to treat human diseases.</p>
<p>THC <a href="https://doi.org/10.1038/sj.bjp.0706406">was first identified</a> in 1964, and is just one of more than 100 compounds found in marijuana that are <a href="https://www.cdc.gov/marijuana/health-effects/index.html">called cannabinoids</a>.</p>
<p><a href="https://doi.org/10.1016/j.tips.2015.02.008">Endocannabinoids were not discovered</a> until 1992. Since then, research has revealed that they are critical for many important physiological functions that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/">regulate human health</a>. An imbalance in the production of endocannabinoids, or in the body’s responsiveness to them, <a href="https://doi.org/10.1111%2Ffebs.12260">can lead to major clinical disorders</a>, including obesity as well as neurodegenerative, cardiovascular and inflammatory diseases. </p>
<p>We <a href="https://scholar.google.com/citations?user=jJVj3sUAAAAJ&hl=en">are immunologists</a> who have been <a href="https://scholar.google.com/citations?user=af7TahQAAAAJ&hl=en">studying the effects of marijuana cannabinoids and vertebrate endocannabinoids</a> on inflammation and cancer for more than two decades. <a href="https://doi.org/10.1016%2Fj.phrs.2009.03.019">Research in our laboratory</a> has shown that endocannabinoids <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">regulate inflammation</a> and other immune functions. </p>
<h2>What is the endocannabinoid system?</h2>
<p>A variety of tissues in the body, including brain, muscle, fatty tissue and immune cells, <a href="https://pubmed.ncbi.nlm.nih.gov/19675519/">produce small quantities of endocannabinoids</a>. There are <a href="https://doi.org/10.1016/j.phrs.2009.03.019">two main types of endocannabinoids</a>: anandamide, or AEA, and 2-arachidonoyl glycerol, known as 2-AG. Both of them can activate the body’s cannabinoid receptors, which receive and process chemical signals in cells. </p>
<p>One of these receptors, called CB1, is <a href="https://doi.org/10.3390%2Fijms19030833">found predominantly in the brain</a>. The other, called CB2, is <a href="https://doi.org/10.4155/fmc.09.93">found mainly in immune cells</a>. It is primarily through the activation of these two receptors that endocannabinoids control many bodily functions.</p>
<p>The receptors can be compared to a “lock” and the endocannabinoids a “key” that can open the lock and gain entry into the cells. All these endocannabinoid receptors and molecules together are referred to as the endocannabinoid system. </p>
<p>The cannabis plant contains another compound called cannabidiol, or CBD, which has <a href="https://theconversation.com/cbd-is-not-a-cure-all-heres-what-science-says-about-its-real-health-benefits-186901">become popular</a> for its medicinal properties. Unlike THC, CBD doesn’t have psychoactive properties because it <a href="https://doi.org/10.1146%2Fannurev-neuro-070815-014038">does not activate CB1 receptors in the brain</a>. Nor does it <a href="https://doi.org/10.1038/sj.bjp.0707442">activate the CB2 receptors</a>, meaning that its action on immune cells is independent of CB2 receptors. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Textbook illustration of the human endocannabinoid system, highlighting the role of CB1 and CB2 receptors." src="https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=960&fit=crop&dpr=1 600w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=960&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=960&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1206&fit=crop&dpr=1 754w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1206&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1206&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Endocannabinoid receptors are found throughout most of the human body.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/human-endocannabinoid-system-vertical-royalty-free-illustration/1178997969">About time/iStock via Getty Images Plus</a></span>
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<h2>Role of endocannabinoids in the body</h2>
<p>The euphoric “high” feeling that people experience when using marijuana comes from THC activating the CB1 receptors in the brain. </p>
<p>But when endocannabinoids activate CB1 receptors, by comparison, they do not cause a marijuana high. One reason is that the body <a href="https://doi.org/10.1038/npp.2017.130">produces them in smaller quantities</a> than the typical amount of THC in marijuana. The other is that <a href="https://doi.org/10.1021%2Fcr0782067">certain enzymes break them down</a> rapidly after they carry out their cellular functions.</p>
<p>However, there is growing evidence that certain activities may release mood-elevating endocannabinoids. Some research suggests that the relaxed, euphoric feeling you get after exercise, called a “<a href="https://theconversation.com/the-runners-high-may-result-from-molecules-called-cannabinoids-the-bodys-own-version-of-thc-and-cbd-170796">runner’s high</a>,” results from the <a href="https://www.scientificamerican.com/article/new-brain-effects-behind-runner-s-high/">release of endocannabinoids</a> <a href="https://runningmagazine.ca/health-nutrition/new-study-confirms-endorphins-arent-the-cause-of-the-runners-high/">rather than from endorphins</a>, as previously thought.</p>
<p>The endocannabinoids <a href="https://doi.org/10.3390/ijms22179472">regulate several bodily functions</a> such as sleep, mood, appetite, learning, memory, body temperature, pain, immune functions and fertility. They control some of these functions by regulating nerve cell signaling in the brain. Normally, nerve cells communicate with one another at junctions called synapses. The endocannabinoid system in the brain regulates this communication at synapses, which explains its ability to affect a wide array of bodily functions. </p>
<h2>The elixir of endocannabinoids</h2>
<p>Research in our laboratory has shown that <a href="https://doi.org/10.1002/eji.201546181">certain cells of the immune system produce endocannabinoids</a> that can regulate inflammation and other immune functions through the activation of CB2 receptors.</p>
<p>In addition, we have shown that <a href="https://doi.org/10.1124/mol.108.047035">endocannabinoids are highly effective in lessening the debilitating effects of autoimmune diseases</a>. These are diseases in which the immune system goes haywire and <a href="https://medlineplus.gov/autoimmunediseases.html">starts destroying the body’s organs and tissues</a>. Examples include <a href="https://medlineplus.gov/multiplesclerosis.html">multiple sclerosis</a>, <a href="https://doi.org/10.1124/mol.108.047035">lupus</a>, <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/hepatitis">hepatitis</a> and <a href="https://www.niams.nih.gov/health-topics/arthritis">arthritis</a>. </p>
<p>Recent research suggests that migraine, fibromyalgia, irritable bowel syndrome, post-traumatic stress disorder and bipolar disease are all <a href="https://doi.org/10.1089/can.2016.0009">linked to low levels of endocannabinoids</a>.</p>
<p>In a 2022 study, researchers found that a defect in a gene that helps produce endocannabinoids causes <a href="https://doi.org/10.1038/s41467-022-31168-9">early onset of Parkinson’s disease</a>. Another 2022 study linked the same gene defect to <a href="https://doi.org/10.1093/brain/awac223">other neurological disorders</a>, including developmental delay, poor muscle control and vision problems. </p>
<p>Other research has shown that people with a defective form of CB1 receptors <a href="https://doi.org/10.1371/journal.pone.0187926">experience increased pain sensitivity</a> such as migraine headaches and suffer from sleep and memory disorders and anxiety. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=495&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=495&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=495&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=622&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=622&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=622&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The endocannabinoid system – consisting of the endocannabinoids and the cannabinoid receptors – regulates nerve cell communication at the synapse, thereby playing a role in a variety of bodily functions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/endocannabinoid-system-royalty-free-illustration/1392987232?phrase=endocannabinoid%20system&adppopup=true">Carolina Hrejsa, CMI/iStock/Getty Images Plus via Getty Images</a></span>
</figcaption>
</figure>
<h2>The likeness between marijuana and endocannabinoids</h2>
<p>We believe that the medicinal properties of THC may be linked to the molecule’s ability to compensate for a deficiency or defect in the production or functions of the endocannabinoids. </p>
<p>For example, scientists have found that people who experience certain types of chronic pain may have <a href="https://doi.org/10.3390/molecules27144662">decreased production of endocannabinoids</a>. People who consume marijuana for medicinal purposes <a href="https://www.nationalacademies.org/news/2017/01/health-effects-of-marijuana-and-cannabis-derived-products-presented-in-new-report">report significant relief from pain</a>. Because the THC in marijuana <a href="https://dx.doi.org/10.1001/jama.2018.16202">is the cannabinoid that reduces pain</a>, it may be helping to compensate for the decreased production or functions of endocannabinoids in such patients. </p>
<p>Deciphering the role of endocannabinoids is still an emerging area of health research. Certainly much more research is needed to decipher their role in regulating different functions in the body. </p>
<p>In our view, it will also be important to continue to unravel the relationship between defects in the endocannabinoid system and the development of various diseases and clinical disorders. We think that the answers could hold great promise for the development of new therapies using the body’s own cannabinoids.</p><img src="https://counter.theconversation.com/content/198220/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Institutes of Health and the National Science Foundation. </span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from National Institutes of Health. </span></em></p>A THC-like substance that occurs naturally in humans and other vertebrates helps maintain immunity, memory, nerve function and more – and research suggests a lack of it can harm health.Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1923742022-10-19T12:38:41Z2022-10-19T12:38:41ZColonoscopy is still the most recommended screening for colorectal cancer, despite conflicting headlines and flawed interpretations of a new study<figure><img src="https://images.theconversation.com/files/490183/original/file-20221017-7171-u96cve.jpg?ixlib=rb-1.1.0&rect=7%2C14%2C4812%2C3598&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Colorectal cancer is the second-leading cause of cancer death. But by finding polyps early on, colonoscopies can detect and prevent the cancer.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/polyp-found-during-a-colonoscopy-artwork-royalty-free-illustration/513096193?phrase=colonoscopies&adppopup=true">Sebastian Kaulitzki/Science Photo Library via Getty Images</a></span></figcaption></figure><p>A recently published study in a high-profile medical journal appeared to call into question <a href="https://doi.org/10.1056/NEJMoa2208375">the efficacy of colonoscopy</a>, a proven and widely utilized strategy for the screening and prevention of colorectal cancer. </p>
<p>News headlines were striking: “<a href="https://doi.org/10.1038/d41586-022-03228-z">Disappointing results on colonoscopy benefits</a>”; “<a href="https://thehill.com/policy/healthcare/3681186-new-study-suggests-benefits-of-colonoscopies-may-be-overestimated/">New study suggests benefits of colonoscopies may be overestimated</a>”; “<a href="https://www.statnews.com/2022/10/09/in-gold-standard-trial-colonoscopy-fails-to-reduce-rate-of-cancer-deaths/">In gold-standard trial, invitation to colonoscopy reduced cancer incidence but not death</a>.”</p>
<p>Such news coverage has ignited controversy and created some confusion about the study and its implications, leading people to question whether the results suggest that reevaluation of the utility and need for a colonoscopy is warranted. </p>
<p>As a <a href="https://sc.edu/study/colleges_schools/artsandsciences/biological_sciences/our_people/directory/berger_franklin.php">cancer research scientist</a> with over 20 years of experience studying colorectal cancer screening and prevention, I am confident that colonoscopy remains one of the most critical and effective tools to screen for, detect and prevent this prevalent and lethal form of cancer. </p>
<p>Colorectal cancer is the fourth-most prevalent and second-leading cause of cancer deaths in the U.S. The American Cancer Society estimates that there will be <a href="https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html">151,000 new cases of colorectal cancer</a> diagnosed in 2022 and nearly 53,000 deaths. Screening has contributed markedly <a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2020-2022.pdf">to a decline</a> in colorectal cancer cases and deaths over the past several decades. </p>
<p>Current <a href="https://doi.org/10.1001/jama.2021.6238">U.S. Preventive Services Taskforce guidelines</a> recommend that people with average risk begin screening for colorectal cancer at the age of 45. This recommendation was <a href="https://theconversation.com/colorectal-cancer-screening-recommended-at-age-45-instead-of-50-its-no-fun-but-its-worth-it-155214">lowered from age 50</a> in 2021 due to the recent increase in colorectal cancer disease <a href="https://doi.org/10.1056/NEJMra2200869">prevalence among young adults</a>. </p>
<figure>
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<figcaption><span class="caption">Although there are numerous ways to screen for colon cancer, a colonoscopy remains the most comprehensive way to test.</span></figcaption>
</figure>
<h2>Unpacking the new study</h2>
<p>Several investigations have shown that colonoscopy screening is <a href="https://doi.org/10.1001/jama.2021.6238">highly effective</a> in the detection and removal of precancerous polyps before they progress to cancer. </p>
<p>That is why media coverage of the new study published in the New England Journal of Medicine prompted confusion and concern among health care experts and the public. Many of these news reports mistakenly interpreted the study as showing that colonoscopies have a small effect on the incidence of colorectal cancer and are ineffective at reducing deaths. Such misinterpretations could have grave consequences with regard to efforts aimed at screening and preventing a form of cancer that affects the health and well-being of so many.</p>
<p>In the study, a team of European researchers performed a randomized clinical trial that examined the risk of colorectal cancer and death in healthy men and women between the ages of 55 and 64. Study participants, who were recruited from population registries in Norway, Sweden, Poland and the Netherlands, were either invited to undergo a colonoscopy or were not invited and received usual care.</p>
<p>After approximately 10 years, the research team gathered information on colorectal cancer incidence and deaths among 28,220 in the invited group and 56,365 in the uninvited group. They found that those in the invited group had a mere 18% decrease in the number of cases of colorectal cancer relative to those in the uninvited group. They also found that there was no significant reduction in deaths in the invited group. This seemingly disappointing result drove many of the more misleading headlines in the media.</p>
<p>But there is a critical caveat in all this that bears explaining. Only 42% of the participants who were invited to receive a colonoscopy did so. This percentage ranged from 33% among those from Poland, from where most of the participants were recruited, to 60.7% among those from Norway. </p>
<p>When the researchers determined the benefit among those who actually underwent a colonoscopy, they found that the incidence of colorectal cancer decreased by 31% and deaths decreased by 50% – results that are much closer to those <a href="https://doi.org/10.1056/NEJMoa1100370">expected from other studies</a>.</p>
<p>Another shortcoming of the study is the time between recruitment and screening of the participants. Colorectal cancer is <a href="https://health.clevelandclinic.org/how-quickly-do-colon-polyps-turn-cancerous/">typically slow to develop</a>, taking 10 or more years to progress from precancerous polyps to cancer. Thus, the 10-year window used in the study may be too short to measure the full impact of colonoscopy screening. The authors recognize this and indicate that they will be doing an analysis at 15 years.</p>
<p>These and other issues have been clearly outlined in responses to the study by several medical and advocacy groups comprised of experts with long-standing experience in colorectal cancer and its screening. These include the <a href="https://nccrt.org/crc-news-october-12-2022/">National Colorectal Cancer Roundtable</a>, the <a href="https://www.ccalliance.org/news/press-releases/statement-colonoscopies-prevent-crc-despite-one-study-headlines">Colorectal Cancer Alliance</a>, the <a href="http://pressroom.cancer.org/CRCScreeningStatement">American Cancer Society</a> and the <a href="https://www.asge.org/home/about-asge/newsroom/news-list/2022/10/10/colonoscopy-remains-best-and-proven-way-to-detect-and-prevent-colorectal-cancer-and-colorectal-cancer-deaths">American Society for Gastrointestinal Endoscopy</a>, among others. </p>
<p>All of the responses emphasize that, despite the tone of much of the media coverage, nothing in the study changes the recognized reliability or efficacy of colonoscopy screening. At best, the findings confirm that for many, a simple invitation to screening does not necessarily promote participation in screening. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/xCmnWsAqMlw?wmode=transparent&start=52" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">What the doctor sees during a colonoscopy – a close-up look.</span></figcaption>
</figure>
<h2>Colonoscopy remains the ‘gold standard’</h2>
<p>During a colonoscopy, a long flexible tube is inserted into the rectum and moved through the colon to allow the direct viewing, identification, imaging and removal of abnormal tissues such as precancerous polyps that could progress into colorectal cancer. As such, for quite some time, colonoscopies have been considered the “gold standard” for colorectal cancer screening and prevention, and still are. </p>
<p>However, there are several features of the procedure that can deter people from choosing it. It is invasive, and there is risk – though small – of <a href="https://doi.org/10.1053/j.gastro.2018.01.010">complications</a>. In addition, for the procedure to be effective, the colon must be cleared of any stool, requiring a protocol that many find distasteful and uncomfortable. Finally, it can be expensive, creating barriers for those who lack adequate insurance coverage.</p>
<p>Though not as sensitive as a colonoscopy, there are a number of <a href="http://nccrt.org/wp-content/uploads/2018ACSCRCGuidelineOverview_FINAL.NCCRT_.8.7.18.pdf">noninvasive alternatives</a> for colorectal cancer screening that are currently available and recommended by the <a href="https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening">U.S. Preventive Services Task Force</a> for people with normal risk levels. Such alternatives include stool tests such as <a href="https://www1.nyc.gov/assets/doh/downloads/pdf/cancer/fobt-fact-sheet.pdf">high-sensitivity guaiac fecal occult blood tests</a>, <a href="https://medlineplus.gov/ency/patientinstructions/000704.htm">fecal immunochemical tests</a> and <a href="https://doi.org/10.1056/NEJMoa1311194">multitarget stool DNA tests</a>. </p>
<p>These methods vary in effectiveness, and each has advantages and disadvantages. The option of choice is based upon patient preference, determined with input from the medical provider. But those at higher risk, such as having a family history of colorectal cancer, certain symptoms such as blood in the stool or a history of polyps are <a href="https://doi.org/10.1001/jama.2021.6238">advised to get screened by a colonoscopy</a>.</p>
<p>Importantly, noninvasive screening tests do not on their own prevent the disease. Rather, they raise the possibility that a benign polyp or tumor may exist, and must therefore be followed up with a colonoscopy to confirm the presence of, and remove, any abnormal lesions. </p>
<h2>New directions for cancer screening</h2>
<p>Most recently, researchers have made significant progress in the development of <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2017/liquid-biopsy-detects-treats-cancer">liquid biopsies</a>, which involve the profiling of informative biomarkers in fluids such as blood. This type of profiling identifies signals for detecting and monitoring numerous cancers, including colorectal cancer. </p>
<p>There is particular enthusiasm in the scientific and medical communities around liquid biopsies that can aid in <a href="https://doi.org/10.1016/j.ccell.2022.01.012">multi-cancer early detection</a>. This approach offers great potential in the early detection of colorectal cancer as well as numerous other cancers for which there are currently no effective screening methods. Multi-cancer early detection tests are under development by many companies and are not yet approved by the Food and Drug Administration. Several are <a href="https://www.galleri.com/hcp/the-galleri-test/ordering">currently available</a> by prescription as laboratory-developed tests.</p>
<p>As with all noninvasive tests, liquid biopsies must be appropriately followed up to verify, remove and/or treat any identified lesions. Extensive research on liquid biopsies is ongoing, and results suggest that a new generation of highly sensitive, readily available and patient-friendly modes of cancer screening will emerge in the next few years.</p>
<p>Over the past several decades, screening has contributed significantly to a marked reduction in the incidence and mortality of colorectal cancer. Given the aging of the population, as well as the <a href="https://doi.org/10.1056/NEJMra2200869">recent rise in colorectal cancer</a> among young adults, detecting the disease sensitively and in its earliest stages is more important than ever.</p><img src="https://counter.theconversation.com/content/192374/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Franklin G. Berger receives funding from Centers for Disease Control & Prevention</span></em></p>Don’t be confused by recent media reports – colonoscopies are still the best way to detect and prevent colon cancer.Franklin G. Berger, Distinguished Professor Emeritus of Biological Sciences, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1783812022-05-30T12:27:57Z2022-05-30T12:27:57ZRace, gender and the ways these identities intersect matter in cancer outcomes<figure><img src="https://images.theconversation.com/files/463462/original/file-20220516-11-3il8v8.jpg?ixlib=rb-1.1.0&rect=43%2C51%2C5708%2C3742&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cancer care research usually focuses on just one of a patient's social identities.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/patients-in-infusion-room-royalty-free-image/522902646">Isaac Lane Koval/Corbis/VCG via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em> </p>
<h2>The big idea</h2>
<p>Belonging to one or more groups with long-standing social and economic disadvantages increases the risk of cancer diagnoses and death, according to <a href="https://doi.org/10.1002/pon.5890">our review of 28 cancer studies</a> published between 2012 and 2021. </p>
<p>People who were both nonwhite and LGBTQ <a href="https://doi.org/10.1002/pon.5890">received fewer cancer</a> prevention services and had fewer cancer screenings, we found, for example. </p>
<p>We started by searching for studies of groups with poor cancer outcomes. Then we narrowed our focus to cancer studies that specified the race, sexual orientation, gender identity, socioeconomic status, disability status or rural residency of study participants. We found just 28 that provided such information. We classified those studies according to the aspect of cancer care they covered. Some studies, for example, were about <a href="https://doi.org/10.1016/j.socscimed.2014.06.039">cancer screening and prevention</a>, while others <a href="https://doi.org/10.1245/s10434-020-09267-y">focused on treatment</a>. </p>
<p>Most of the studies focused on what people did to prevent cancer or to check for it. Examples include getting mammograms or a human papilloma virus vaccine. And we found some studies that were about specific kinds of cancer, like cervical or breast.</p>
<p>We found that sexual orientation and race influenced whether women chose to get screened for cancer or to take preventive treatments. Nonwhite women of low socioeconomic status also had lower cancer survival rates. We saw that these patients experienced fears of discrimination, a general discomfort with health care providers and more distrust of the health care system. </p>
<h2>Why it matters</h2>
<p>Despite advances in detection and treatment, <a href="https://www.cdc.gov/cancer/dcpc/research/update-on-cancer-deaths/index.htm">cancer remains the second-leading cause of death in the United States</a>. And in communities with long-standing social and economic disadvantages, the risk of cancer diagnoses and death is higher than in the general population.</p>
<p>For example, Black women are <a href="https://doi.org/10.1136/bmj.a586">more likely than white women</a> to die of breast cancer. New diagnoses of prostate cancer occur more frequently <a href="https://www.cancer.gov/about-cancer/understanding/disparities">in rural Appalachia</a>, compared with urban areas in the same region. And bisexual women are 70% more likely to get a cancer diagnosis, <a href="https://www.cancer.gov/about-cancer/understanding/disparities">compared with heterosexual women</a>.</p>
<p>Cancer care research usually overlooks the multiple identities of individual patients. But most people have more than one social identity, and those identities are hard to separate from one another. For example, a gay Black man is not gay one day and Black the next; he’s both, all the time. And he has different experiences of discrimination and disadvantage compared with a straight Black man. </p>
<p><a href="https://theconversation.com/intersectionality-how-gender-interacts-with-other-social-identities-to-shape-bias-53724">Intersectionality describes</a> the recognition and consideration of a person’s multiple, intersecting social identities. Taking these multiple identities into consideration could help improve cancer prevention and survival among those who belong to one or more historically disadvantaged groups. </p>
<h2>What still isn’t known</h2>
<p>We did not look at lifestyle behaviors, such as smoking, that could increase the risk of getting cancer and contribute to poorer cancer treatment outcomes. However, cancer <a href="https://www.cancer.gov/about-cancer/understanding/disparities">disparities based on lifestyle behaviors</a> are well documented, and it would be valuable to look at how complex identities and lifestyle affect those outcomes.</p>
<p>As researchers we wanted to focus on identifying studies in the literature that focused on the interconnected, multiple ways patients self-identify and how this related to their health care. Unfortunately, only a small amount of data was available, and our current report suffered from these limitations.</p>
<h2>What’s next</h2>
<p>Our paper describes ways for scientists to take patients’ multiple identities into account when doing cancer research. This model includes recommendations for setting up studies, conducting the research itself and documenting the findings. Considering more complex patient identities could make future studies more consistent and understandable. It will help fill some large gaps we’re seeing in how researchers study cancer.</p><img src="https://counter.theconversation.com/content/178381/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Belonging to one or more groups with long-standing social and economic disadvantages increases the risk of cancer diagnoses and death.Timothy Pawlik, Professor of Surgery, The Ohio State UniversityElizabeth Palmer, Research Scientist, The Ohio State UniversitySamilia Obeng-Gyasi, Assistant Professor of Surgical Oncology, The Ohio State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1824002022-05-23T12:22:52Z2022-05-23T12:22:52ZCancer groundshot: Access to proven treatments must parallel development of new therapies<figure><img src="https://images.theconversation.com/files/464445/original/file-20220520-20-9y62l9.jpg?ixlib=rb-1.1.0&rect=476%2C233%2C4994%2C3601&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cancer groundshot highlights that investment in improving access to treatments already proven to work saves more lives than discovery of a new treatment.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Where should investment be made today in order to save the maximum number of lives from cancer tomorrow? That is the underlying principle behind the “<a href="https://doi.org/10.1016/S1470-2045(18)30076-7">cancer groundshot</a>” philosophy.</p>
<p>Annually, billions of dollars are spent on ambitious “<a href="https://doi.org/10.1038/d41586-022-00376-0">cancer moonshot</a>” programs. These programs focus on the discovery of new drugs and technologies aimed at solving the cancer burden. The hope is that discovery of a new target, a new drug or a new mechanism will help to cure cancer or reduce the cancer burden. </p>
<p>The United States’ ambitious Cancer Moonshot program marks its fifth anniversary in 2022, and certainly, cancer is still very much a global problem that needs addressing. Some new drugs have been developed in this time frame, but the <a href="https://dx.doi.org/10.1001%2Fjamaoncol.2018.1660">percentage of patients</a> who has benefited from these newer drugs has <a href="https://doi.org/10.1001/jamanetworkopen.2019.2535">remained small</a>. </p>
<p>Globally, most patients with cancer die not because they don’t have access to these newer drugs, but because they do not have access to even the basic treatments. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A man in a suit at a podium beside a blue display reading 'Cancer Moonshot'" src="https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/463052/original/file-20220513-14-eo9b54.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">President Joe Biden speaks during a Cancer Moonshot event at the White House on Feb. 2, 2022.</span>
<span class="attribution"><span class="source">(AP Photo/Alex Brandon)</span></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.1016/j.clon.2014.10.006">More than 90 per cent of patients in low-income countries, and more than half of patients in low- and middle-income countries,</a> do not have access to basic radiotherapy services. <a href="https://doi.org/10.1016/s1470-2045(15)00223-5">More than half of patients globally who need cancer surgery</a> will go without, and services needed for accurate cancer diagnosis are lacking. </p>
<p>These are interventions that help cure cancer and save the most lives, as opposed to newer drugs that only marginally extend survival or delay cancer growth. If inequity in access to proven effective interventions persists, newer treatment options will not reduce global cancer burden.</p>
<h2>Cancer groundshot</h2>
<p>I coined the term <a href="https://ecancer.org/en/news/10659-last-month-in-immuno-oncology-with-dr-bishal-gyawali-november-2016">“cancer groundshot” in 2016 in a blog post</a> to encourage prioritization in cancer care and research. It is a part of the <a href="https://doi.org/10.1038/s41591-021-01662-6">common-sense revolution in oncology</a>. </p>
<p>Cancer groundshot highlights that investing in improved access to interventions already proven to work saves more lives than discovery of a new intervention. When patients are dying due to lack of access to surgery or accurate diagnosis, a new cancer drug is not going to solve the problem. </p>
<p>Cervical cancer is a good example. It is probably the only cancer for which <a href="https://www.who.int/publications/i/item/9789240014107">elimination is a realistic goal</a>. HPV vaccination, cervical cancer screening and effective treatment of early detected cervical cancers may help us eliminate this cancer. </p>
<p>At the same time, newer drugs like <a href="https://doi.org/10.1056/NEJMoa2112435">pembrolizumab reportedly improve two-year survival rates</a> in metastatic cervical cancer by 10 percentage points. While not discounting this medical advancement, it is more prudent for countries around the world to invest in cervical cancer screening, HPV vaccination and early treatment, rather than investing in access to pembrolizumab (one year of this drug <a href="https://www.fiercepharma.com/pharma/updated-merck-s-melanoma-game-changer-keytruda-likely-to-bolster-drug-pricing-debate">costs roughly US$150,000</a>). </p>
<p>In this example, the use of pembrolizumab represents the cancer moonshot approach to cervical cancer. Focusing on vaccination, screening and early treatment represents the cancer groundshot approach.</p>
<h2>Costs and priorities</h2>
<p>The cost of pembrolizumab is not an outlier. Modern cancer treatments are quite expensive. On average, based on 2018 data, a new cancer drug costs <a href="https://doi.org/10.1001/jamainternmed.2020.5921">more than US$150,000 per patient per year</a>. On the other hand, barring a few good drugs, the benefits these drugs provide are <a href="https://doi.org/10.1001/jamainternmed.2020.8588">not very impressive on average</a>. For example, some new cancer drugs <a href="https://doi.org/10.1038/s41571-021-00504-1">delay progression by a median of only three days</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A boy in a hat with an IV line in his arm sits at a table drawing with a woman wearing a face mask as another child looks on" src="https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/464441/original/file-20220520-11-plryu4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Children play as they receive treatment at the cancer ward of the Children’s Hospital in March, in Damascus, Syria, where more than a decade of war has brought the Syrian health sector close to collapse, and cancer treatment is often unaffordable or in short supply.</span>
<span class="attribution"><span class="source">(AP Photo/Omar Sanadiki)</span></span>
</figcaption>
</figure>
<p>Although valuation of life is inherently an impossible task, I think as a society we can agree that our resources can be better allocated than spending $16,000 per month for delaying tumour growth by three days. <a href="https://doi.org/10.1001/jamaoncol.2022.0864">A new study</a> shows that these extra days of delayed tumour growth may not necessarily mean good quality of life, either. </p>
<p>Cancer groundshot is a philosophy that calls for prioritization of strategies in global cancer control. The underlying principle of cancer groundshot is that one must ensure access to interventions that are already proven to work before focusing on the development of new interventions. We need to realign our priorities and invest on equitable access to high-value interventions. </p>
<p>This is not only an issue in low- and middle-income countries. Severe disparities in access to care exist within high-income countries as well. There are several pockets of population in countries like the <a href="https://www.cancer.gov/about-cancer/understanding/disparities">United States</a> and <a href="https://dx.doi.org/10.3747%2Fco.19.1177">Canada</a>, that are underserved and lack access to timely and adequate cancer care. There are disparities in socio-economic status, awareness levels, insurance coverage and other <a href="https://www.doi.org/10.25318/82-003-x202100600002-eng">factors that lead to differential outcomes, even within the same country</a>. </p>
<h2>Advocacy and implementation</h2>
<p>I laid out the details of the cancer groundshot philosophy in a <a href="https://doi.org/10.1016/S1470-2045(18)30076-7">2018 paper in the journal <em>Lancet Oncology</em></a>. Since then, it has been gaining momentum in the cancer policy world. I have spoken about this at several international and national meetings, and this concept has been discussed both in academia and beyond. This year at the <a href="https://meetinglibrary.asco.org/session/14456">Annual Meeting of the American Society of Clinical Oncology</a> (ASCO), the world’s largest oncology conference, I am chairing a session on cancer groundshot. </p>
<p>This recognition from ASCO will certainly add to its recognition, and hopefully, adoption. The session is organized into three talks, which have also been compiled into a <a href="https://ascopubs.org/doi/full/10.1200/EDBK_359521">book chapter</a>: </p>
<ul>
<li><p>Cancer groundshot and how clinical trials fit into this philosophy.</p></li>
<li><p>Disparities in low- and middle-income countries, and if technology can help address this challenge.</p></li>
<li><p>Disparities in cancer care within high-income countries.</p></li>
</ul>
<p>However, the real metric for the cancer groundshot is implementation of the philosophy and reduction in the inequities in access to proven therapies. Advocacy is the first step to achieve that end.</p><img src="https://counter.theconversation.com/content/182400/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bishal Gyawali receives funding from Ontario Institute for Cancer Research and Conquer Cancer Foundation. </span></em></p>Globally, most cancer patients die not because they don’t have access to newer drugs, but because they don’t have access to even basic treatments. Cancer groundshot aims to improve treatment access.Bishal Gyawali, Associate Professor of Oncology and Public Health Sciences, Queen's University, OntarioLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1308302020-01-31T13:09:15Z2020-01-31T13:09:15ZLung cancer: quitting smoking regrows protective lung cells – new research<figure><img src="https://images.theconversation.com/files/313050/original/file-20200131-41532-16kwzup.jpg?ixlib=rb-1.1.0&rect=15%2C7%2C5184%2C3266&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The findings show it's never too late to quit.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/stop-smoking-382326067">Nuttaphong Sriset/ Shutterstock</a></span></figcaption></figure><p>We know that <a href="https://www.who.int/tobacco/quitting/benefits/en/">quitting smoking</a> is an <a href="https://www.bmj.com/content/321/7257/323">excellent way to reduce your risk</a> of developing lung cancer. But until now, experts weren’t quite sure why this was the case. Our <a href="https://www.nature.com/articles/s41586-020-1961-1">latest research</a> has uncovered that in people who quit smoking, the body actually replenishes the airways with normal, non-cancerous cells that help protect the lungs, in turn reducing their risk of getting cancer. </p>
<p>Cancer develops when a single rogue cell acquires genetic changes, called mutations, that instruct that cell to ignore all the normal constraints on its growth, <a href="https://www.nature.com/articles/nature07943">causing it to rapidly replicate out of control</a>. Throughout our lives, all of our cells acquire mutations at a steady rate – <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536223/">around 20-50 mutations per cell per year</a>. Thankfully, the vast majority of these mutations are entirely harmless and don’t affect our cells in any measurable way. </p>
<p>But occasionally, a mutation will land in the wrong gene in the wrong cell and push the cell along the path to cancer. We call these genetic changes <a href="https://www.nature.com/articles/nature07943">“driver mutations”</a>. For the cell to become a full-blown cancer cell, it would probably need <a href="https://www.cell.com/cell/fulltext/S0092-8674(17)31136-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867417311364%3Fshowall%3Dtrue">five to ten or more of these driver mutations</a>. </p>
<p>Thanks to advances in DNA sequencing technology, we’re now able to study all 3 billion bases of DNA that make up a cell’s genetic blueprint (called a genome). By sequencing the DNA of lung cancer cells in smokers and never-smokers, we know that smoking increases the number of mutations.</p>
<p>The binding of tobacco carcinogens to DNA is influenced by their chemical properties, meaning that certain types of mutation are more likely to occur than other types. For tobacco, this results in a distinctive <a href="https://www.nature.com/articles/nature08629">“signature” of mutations</a> appearing in the genome, which is unlike other causes of DNA damage.</p>
<p>Our team has been interested in the very earliest stages of lung cancer development. Specifically, we’re trying to understand what happens to normal cells when they’re exposed to tobacco smoke.</p>
<p>To study this, we developed methods of isolating single normal cells from small biopsies of a patient’s airways, then growing these cells in an incubator to obtain enough DNA for sequencing. We then <a href="https://www.nature.com/articles/s41586-020-1961-1">analysed the genomes of 632 cells</a> from 16 study participants including four never-smokers, six ex-smokers and three current smokers (all middle-aged or older) as well as three children. </p>
<p>Among the never-smokers, we found that the number of cell mutations increased steadily with age. So, by the time someone is 60 years old, each normal lung cell will contain about 1,000-1,500 mutations. These mutations are caused by the normal wear-and-tear of life, the same type of mutations we see in other organs in the body. Only about 5% of cells in never-smokers were found to have any driver mutations.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313051/original/file-20200131-41527-ljwqg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Driver mutations are what cause cells to become cancerous.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/digital-illustration-lung-cancer-cells-color-233501644">RAJ CREATIONZS/ Shutterstock</a></span>
</figcaption>
</figure>
<p>But the picture was very different in current smokers. We found that each lung cell on average carried an extra 5,000 mutations above what we would expect for a never-smoker of the same age. Even more striking was that the variation from cell to cell also dramatically increased in smokers.</p>
<p>Some individual cells had 10,000-15,000 mutations – ten times more mutations than we would expect if the person hadn’t smoked. These extra mutations had the signature we would expect from the chemicals in tobacco smoke, confirming that they can be directly attributed to cigarettes.</p>
<p>Alongside an increase in the total number of mutations, we also saw a substantial increase in the number of driver mutations. More than a quarter of lung cells in all the current smokers we studied had at least one drive mutation. Some even had two or three. Given that five to ten of these kind of mutations can caused cancer, it’s clear that many normal lung cells in these middle-aged or older smokers will likely become cancerous. </p>
<h2>Never too late to quit</h2>
<p>Our most exciting finding was in the people who had quit smoking. We found ex-smokers had two groups of cells. One group had the thousands of extra mutations seen in current smokers, but the other group were essentially normal. The group of normal cells had the same number of mutations as we would expect to see in the cells of someone who had never smoked.</p>
<p>This near normal group of cells was four times larger in ex-smokers than current smokers. This suggests that these cells increase to replenish the lining of airways after someone stops smoking. We could see this expansion of near-normal cells even in ex-smokers who had smoked a packet of cigarettes every day for more than 40 years.</p>
<p>The reason this finding is so exciting is that this near-normal group of cells protects against cancer. If we study a lung cancer cell from an ex-smoker, it always comes from the <a href="https://www.cell.com/cell/fulltext/S0092-8674(12)01061-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867412010616%3Fshowall%3Dtrue">heavily damaged group of cells</a> – not from the near-normal group.</p>
<p>Now, we know the reason our risk of cancer decreases so significantly is because the body replenishes the airways with cells that are essentially normal. The next step will be to identify how this group of cells manages to avoid damage from exposure to cigarette smoke – and how we might stimulate them to recover even more.</p>
<p>One potential explanation – suggested by past work in <a href="https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30123-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590918301231%3Fshowall%3Dtrue">mouse models</a> – is that there’s a group of stem cells buried deep in the glands that produce the mucus secreted by the airways. This location would naturally be better protected from tobacco smoke than the surface of airways. </p>
<p>For now, our research reiterates that stopping smoking – at any age – not only slows the accumulation of further damage, but it can reawaken cells that haven’t been damaged by past lifestyle choices.</p><img src="https://counter.theconversation.com/content/130830/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sam Janes receives funding from Wellcome and CRUK relevant to this work</span></em></p><p class="fine-print"><em><span>Peter Campbell receives funding from the Mutographs project, a Grand Challenge funded by Cancer Research UK, and the Wellcome Trust relevant to this work.</span></em></p>The study found that ex-smokers had four times the amount of “normal” protective cells than smokers.Sam Janes, Professor of Respiratory Medicine, UCLPeter Campbell, Head of Cancer, Ageing and Somatic Mutation, Wellcome Trust Sanger InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1210572019-08-19T11:26:09Z2019-08-19T11:26:09ZTissue donations are important to cancer research, what happens to your cells after they are taken?<figure><img src="https://images.theconversation.com/files/288499/original/file-20190819-123716-q1lhh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-scientist-looking-through-microscope-laboratory-1081663553?src=MdQfNCBQrSB7eN6JDTiZVw-1-15">Vladimir Borovic/Shutterstock</a></span></figcaption></figure><p>If you’ve ever had a tumour removed or biopsy taken, you may have contributed to <a href="https://theconversation.com/its-time-to-rethink-how-we-do-cancer-research-88048">life-saving research</a>. People are often asked to give consent for any tissue that is not needed for diagnosis to be used in other scientific work. Though you probably won’t be told exactly what research your cells will be used for, tissue samples like these are <a href="https://theconversation.com/more-people-can-donate-tissue-than-organs-so-why-do-we-know-so-little-about-it-31270">vital for helping us understand and improve</a> diagnosis and treatment of a whole range of illnesses and diseases. But once they’re removed, how are these tissue samples used exactly? How do they go from patient to project?</p>
<p>When tissue is removed from a person’s body, most often it is immediately put into a chemical preservative. It is then taken to a lab and embedded in a wax block. Protecting the tissue like this retains its structure and stops it from decomposing so it can be stored at room temperature for long periods of time. </p>
<p>This process also means that biochemical molecules like protein and DNA are preserved, which can provide vital clues about what processes are occurring in the tissue at that stage in the person’s illness. If we were looking at, for example, whether <a href="https://theconversation.com/how-understanding-breast-cancer-at-a-molecular-level-is-revolutionising-our-thinking-42225">molecule A occurs in one particular tumour type</a> but not in others (which would make it helpful for diagnosis) we would want a large number of each type to test. But there may not be enough patients of each type currently in treatment, so it is useful to have a library of samples to draw from. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/more-people-can-donate-tissue-than-organs-so-why-do-we-know-so-little-about-it-31270">More people can donate tissue than organs – so why do we know so little about it?</a>
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</em>
</p>
<hr>
<p>Or we might want to test if patients with tumours containing molecule B are less likely to survive for five years than those without this molecule. This sort of question requires samples with a follow-up time of at least five years. But the answer may help doctors decide whether they need to treat their current patients with B more aggressively or with a <a href="https://theconversation.com/patients-with-exceptional-responses-to-treatment-could-hold-secret-to-new-cancer-cures-60015">different kind of treatment</a>.</p>
<p>To analyse tissues, lab scientists cut very thin slices from the wax blocks and view them under a microscope. The slides are stained with dyes that show the overall tissue structure, and may also be stained with antibodies to show the presence of specific molecules. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/288162/original/file-20190815-136176-xgevww.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Human tissue embedded in wax and a stained slide ready for examination.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/paraffin-box-human-tissue-slide-hemotoxylin-1115636417?src=3qY8Jed7H9AQ57QXFKMvsA-1-1">Komsan Loonprom/Shutterstock</a></span>
</figcaption>
</figure>
<p>Studies often need large numbers of samples from different patients to adequately answer a research question, which can take some time to collect. Take my work for example. My team is interested in finding more about a protein called brachyury, and how it relates to bowel cancer. But to do this we need to compare lots of samples, so we are using tissue from 823 bowel cancer patients and 50 non-cancer patients in our research.</p>
<p>When not in use, the tissue blocks are – with patient consent – placed in a store that researchers can access. The UK has several of these stores, known as biobanks or biorepositories, holding all kinds of tissues. Some cancer biobanks also store different kinds of tumours and blood samples.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-biobanks-can-help-improve-the-integrity-of-scientific-research-100035">How biobanks can help improve the integrity of scientific research</a>
</strong>
</em>
</p>
<hr>
<p>While there are <a href="http://cmpath.ncri.org.uk/wp-content/uploads/2019/06/RPPathApril2019-pages-28-30.pdf">no reliable figures</a> available on how many samples are held in all biobanks, or how often they are used, we do know these numbers are significant. The Children’s Cancer and Leukaemia Biobank alone has banked <a href="https://www.cclg.org.uk/tissue-bank">19,000 samples since 1998</a>. The Northern Ireland Biobank <a href="http://www.nibiobank.org/documents/nres-form-annual-report-for-northern-ireland-biobank-1-april-2017-31-march-2018.pdf">reports that</a> 2,062 patients consented for their tissues to be used in research between 2017-2018, and 4,086 samples were accessed by researchers in that period.</p>
<h2>Identifying biomarkers</h2>
<p>Projects that use biobanks are often trying to identify biomarkers. These are any biological characteristics that give useful information about a disease or condition. Our team is looking at whether the protein brachyury is a useful biomarker to improve bowel cancer diagnosis. </p>
<p>Brachyury is essential for early embryonic development, but it is switched off in most cells by the time you are born. However, <a href="https://www.ncbi.nlm.nih.gov/pubmed/16538613">several studies</a> <a href="https://www.ncbi.nlm.nih.gov/pubmed/26099010">imply that</a> finding brachyury in a tumour indicates a poorer outcome for the patient. But to work out if this link is correct, we need to look at biobank samples. Doing this will help us work out more accurately which patients are at higher risk of cancer recurrence or metastasis. This is important when doctors are deciding on the best course of treatment. </p>
<p>In our research, we also need clinical details, such as what happened to the patient and all the information available at the time of diagnosis. Then we can assess whether testing for brachyury would have added useful information to the diagnosis. Information that accompanies each block is anonymised, which means the researcher analysing the data won’t know the patient’s name or be able to identify them from the sample. But they can see any relevant clinical details such as tumour stage, age, sex and survival. </p>
<p>Biobank samples have had already improved treatment of childhood acute lymphocytic leukaemia. Samples from the Cancer and Leukaemia Biobank were used to demonstrate that children with an abnormality in chromosome 21 had poorer outcomes that those without it. This led to treatment being modified for these children so they are <a href="https://www.ncbi.nlm.nih.gov/pubmed/23940220">no longer at a disadvantage</a>.</p>
<p>People are often applauded for raising money for research by undertaking gruelling or inventive challenges. Patients who decide their tissue can be used in research should be similarly applauded. Without their unique and valuable gift, we wouldn’t be able to further our understanding, diagnosis and treatment of all kinds of illnesses and diseases.</p><img src="https://counter.theconversation.com/content/121057/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Helena Robinson receives funding from Cancer Research Wales. </span></em></p>Donated tissue samples are often used in research to help create new methods of diagnosis and treatment.Helena Robinson, Postdoctoral Research Officer in Cancer Biology, Bangor UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1047432018-10-16T09:52:34Z2018-10-16T09:52:34ZProteins wear clothes – and understanding their fashion choices could help us treat cancer<figure><img src="https://images.theconversation.com/files/240639/original/file-20181015-165924-7hdhws.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/dna-closeup-molecule-model-strands-animation-243535078?src=8cd8_1guT8fOwyn_U89Clw-1-1">UGREEN 3S/ Shutterstock</a></span></figcaption></figure><p>We humans are top of the evolutionary tree, the most complex organisms that have ever lived on Earth in five billion years. Right? One way we might actually prove our biological complexity is to look at the number of different proteins that our bodies can produce for building all our different types of cells and the other things they need.</p>
<p>This number is approximately <a href="https://www.ensembl.org/Homo_sapiens/Info/Annotation">20,418 in humans</a>. We are clearly more complex than <a href="http://www.ensembl.org/Gallus_gallus/Info/Annotation">chickens (18,346)</a>, <a href="http://www.ensembl.org/Drosophila_melanogaster/Info/Annotation">flies (13,931)</a> and <a href="http://science.sciencemag.org/content/326/5957/1235.long">bacteria</a>, some of which can produce only a few hundred different proteins. But here is the humbling news: some crustaceans can make up to <a href="https://metazoa.ensembl.org/Daphnia_pulex/Info/Annotation/">30,000 proteins</a> and a red cabbage has nearly <a href="http://plants.ensembl.org/Brassica_oleracea/Info/Annotation/#assembly">60,000 different proteins</a>.</p>
<p>Scientists have managed to come up with an explanation for this apparent conundrum and save our dignity as a species. One of the features that make us more complex than a cabbage is what’s called post-translational modifications of proteins, the way proteins can change after they are copied from our DNA. If we take these into account, then the total number of different proteins in human cells is an <a href="https://www.hindawi.com/journals/ijac/2016/7436849/">estimated one million</a>.</p>
<p>What’s perhaps more important than showing off to cabbages, however, is the fact that these protein changes, which we here call protein “clothing”, could help us tackle diseases such as cancer. We have developed tiny devices that can analyse the protein clothing <a href="https://www.future-science.com/doi/10.4155/fsoa-2017-0040">in a human tissue sample</a> in a way that could help spot tumours earlier or understand what’s driving them and how best to treat them.</p>
<p>Just like humans, the proteins in our bodies are born without any clothing. But before getting to work and socialising with other proteins, most of them undergo the equivalent of getting dressed. These items of protein clothing can change the “naked” protein’s structure, function and how it interacts with other proteins. So protein clothing contributes hugely to the complexity of our bodies.</p>
<p>The analogy works in different ways. Just as there is only one place where you can (comfortably) wear a left-hand glove and your reading glasses will not work if you put them on your feet, proteins can only wear their modifications at specific sites on their structure <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/pro.3352">for them to work</a>.</p>
<p>Protein modifications can also be reversed. Just as we can take off a jacket if we’re too hot, proteins can have some items of clothing, such as phosphate groups, <a href="https://www.nature.com/articles/ncb3634">removed in a fraction of a second</a>. But other modifications are very stable. For example, if <a href="http://www.nature.com/articles/nrc3409">methyl or lipidic groups</a> are added to proteins they are like “tattoos” that are very difficult to remove.</p>
<p>Again like us, proteins can wear many different items of clothing at the same time. In some cases, these different modifications can interact with each other and also affect what other changes can be <a href="https://link.springer.com/article/10.1007%2Fs00726-014-1890-0">made to the protein</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/240642/original/file-20181015-165888-ndmiwn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/240642/original/file-20181015-165888-ndmiwn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/240642/original/file-20181015-165888-ndmiwn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/240642/original/file-20181015-165888-ndmiwn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/240642/original/file-20181015-165888-ndmiwn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/240642/original/file-20181015-165888-ndmiwn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/240642/original/file-20181015-165888-ndmiwn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Understanding protein ‘clothing’ will help scientists better understand human disease.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/team-research-scientists-working-personal-computer-691546471?src=_5atn6Tru7a97YO9_AUO2A-1-91">Gorodenkoff/ Shutterstock</a></span>
</figcaption>
</figure>
<p>But what does all this have to do with disease? Just as we change our clothing when we’re ill and in hospital, our protein modifications can be very different if we’re suffering from conditions such as cardiovascular disease <a href="https://www.nature.com/articles/nrc3409">and cancer</a>. In these cases, the modifications have gone wrong and the proteins may be wearing the wrong piece of clothing in the wrong place. This can happen with some of the modifications we’ve already mentioned, such as <a href="https://www.nature.com/articles/nrc3409">phosphate and methyl groups</a>.</p>
<p>This means that if we can work out exactly how protein clothing in a tissue sample has gone wrong, then we can understand better what’s going on inside the body. One method we’ve developed to do this is using what we call a <a href="https://www.future-science.com/doi/abs/10.4155/fsoa-2016-0089">cancer-on-chip system</a>. We can place samples taken from a tumour in a microchip-like device about the size of a large coin. Instead of electronic circuits, the chip contains a network of tiny “microfluidic” tubes that can perform a series of chemical experiments on the sample.</p>
<h2>Spotting cancer earlier</h2>
<p>This enables us to recreate the conditions inside the body with a small tissue sample, and without experimenting on animals, to quickly test a variety of standard and new drugs and radiation therapy. Because we can control the conditions of the experiments very precisely, we should be able to investigate which treatment would be best for that specific patient, an approach known as personalised or precision medicine. But cancer-on-chip experiments can also let us investigate the tumour for changes in proteins, including <a href="https://www.ncbi.nlm.nih.gov/pubmed/30216485">post-translational modifications</a>.</p>
<p>This is important because it means we could find new ways to spot cancer by identifying modifications that occur at an early stage. This would allow us to diagnose the disease sooner, giving us a better chance of successfully treating it. Identifying specific modifications could also help us understand the biology of the tumour and the mechanisms causing or driving the cancer.</p>
<p>We’re currently using these cancer-on-chip models to investigate novel disease mechanisms and treatments, and within the next few years we hope to use them in clinical trials with real patients. At which point, we hope that protein clothing will be able to tell us not just about the biological complexity of our species but also the complex conditions that exist inside every one of us.</p><img src="https://counter.theconversation.com/content/104743/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Greenman has received funding from NC3Rs, EPSRC, BBSRC, and Innovate UK for Lab on a Chip projects.</span></em></p><p class="fine-print"><em><span>Pedro Beltran-Alvarez does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The unique way that human proteins change after they are copied from our DNA gives scientists clues about what causes human disease.Pedro Beltran-Alvarez, Lecturer in Biomedical Sciences, University of HullJohn Greenman, Professor of Tumour Immunology, University of HullLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/936332018-04-04T10:47:27Z2018-04-04T10:47:27ZSure, cancer mutates, but it has other ways to resist treatment<figure><img src="https://images.theconversation.com/files/213016/original/file-20180403-189798-16fgd5a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Professor Fabian V. Filipp with his team working on precision targeting of malignant melanoma.</span> <span class="attribution"><span class="source">Systems Biology and Cancer Metabolism Laboratory</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Because of advances in drug design and precision medicine, researchers have been able to target certain molecules within a cell at the root of a particular disease and to develop specific therapies to undo their damages. Today, <a href="https://link.springer.com/article/10.1007%2Fs10555-017-9662-4">precision targeting</a> combines therapy decisions with molecular insights to offer hope after a life-changing cancer diagnosis. </p>
<p>But there’s a dark side to cancer-killing drugs designed to match distinct cancer mutations like a key into a lock. Some cancers that initially respond to targeted chemotherapy become treatment-resistant – and the drug itself may not be the culprit. </p>
<p><a href="https://bmcsystbiol.biomedcentral.com/articles/10.1186/s12918-018-0554-1">New research</a> helps explain how therapy-resistant cancers arise, findings with important implications for the future of cancer therapy. It shows how hidden, subtle layers of regulation – <a href="https://doi.org/10.1093/bfgp/elx001">epigenetics</a> – control the activity of genes to produce drug-resistant surviving cells.</p>
<p>A common feature of cancer across many tumor types is that patients fall back into the state of illness after apparent recovery. My cancer systems biology team at the University of California, Merced, is tackling diagnosis and treatment of therapy-resistant cancers by elucidating the network of changes within cells as a way to identify new drug targets and circumvent cancer resistance.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=314&fit=crop&dpr=1 600w, https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=314&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=314&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=395&fit=crop&dpr=1 754w, https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=395&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/212878/original/file-20180403-189816-1kiddc7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=395&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">High-throughput screening in combination with systems biology analysis identifies cellular control elements and new therapies that overcome drug resistance in malignant melanoma.</span>
<span class="attribution"><span class="source">Systems Biology and Cancer Metabolism Laboratory.</span></span>
</figcaption>
</figure>
<h2>A hidden layer of regulation</h2>
<p>It is well established that <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics">cancer is a disease of our genes</a>. However, resistance to therapy might go beyond cancer mutations that usually alter the function of genes. It may not be new mutations that are causing resistance to drugs. The DNA can stay the same, but cancer cells adapt to therapy and outsmart the drugs by switching their gene activity.</p>
<p>While such adaptations do not affect the DNA itself, a hidden layer of regulation controlling the activity of genes – <a href="https://doi.org/10.18632/oncotarget.15681">epigenetic signals</a> – is responsible for whether cancer cells survive or not, despite the drug a patient is taking. By targeting this hidden program, one can overcome deadly cancer resistance.</p>
<h2>Cancer systems biology reveal new targets and challenges</h2>
<p>To understand how cancer becomes treatment-resistant, my research team at the <a href="https://systemsbiology.ucmerced.edu/">Systems Biology and Cancer Metabolism Lab</a> at UC Merced compared genetic and metabolic pathways in treatment-responsive and treatment-resistant melanomas. <a href="http://dx.doi.org/10.1038/srep07857">Melanoma</a> is a cancer that originates in melanocytes, the cells that produce the skin-color pigment melanin. Though not the most common form of skin cancer, melanoma is the most aggressive. And if it’s not caught and treated early, it’s also among the deadliest.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/213011/original/file-20180403-189821-dtuzfb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Precision medicine is supported by cancer systems biology and big data science. Professor Fabian V. Filipp at the University of California, Merced, is working on cancer genomics to fight therapy-resistant cancers.</span>
<span class="attribution"><span class="source">Systems Biology and Cancer Metabolism Laboratory</span></span>
</figcaption>
</figure>
<h2>Acquired resistance beyond mutations</h2>
<p>Cancer can be triggered by different causes. Melanoma is usually induced by the sun, by dangerous ultraviolet light damage. In the majority of cases, UV damage leaves a unique mutational footprint behind and as a result unstoppable cell proliferation is induced.</p>
<p>UV damage gives rise to point mutations – changes in a single letter of the 3 billion letter human genome. These mutations can <a href="http://dx.doi.org/10.1016/j.neo.2016.01.003">interfere with signals</a> that tell cells when to grow and divide and when to stop. <a href="http://dx.doi.org/10.1038/srep07857">Mutations in a protein called BRAF</a>, a major signaling regulator, cause growth signals to be stuck in the “on” position and drive cancer development.</p>
<p>Though scientists have managed to come up with drugs that target and turn off aberrant BRAF signaling, cancer cells are clever. They learn to adapt to these BRAF-inhibitors. Today, many patients respond to cancer treatment very positively at first. However, unfortunately many ultimately develop resistance and metastases.</p>
<p>Though chemotherapy might kill most of the cancer, tiny populations of drug-resistant cancer cells manage to survive and propagate. Unlike the more familiar case of antibiotic-resistant bacteria, where genetic mutations give rise to resistance, many adaptations in treatment-resistant cancers aren’t the result of mutation.</p>
<h2>Rewiring of gene expression to bypass drug resistance</h2>
<p>Instead, <a href="https://doi.org/10.1038/srep32611">cancer cells adapt to therapy</a> and outsmart the drugs. Melanoma is able circumvent BRAF inhibitors not by changing the genes themselves, but by changing gene activity. Some of the genes with reduced activity were supposed to be in close communication with BRAF and safeguarding its targets, the mutated protein that gave rise to the cancer and the main target of chemotherapy. If essential off switches are lost, they can trigger the tumor cells to divide despite presence of inhibitors.</p>
<p>The resistant cells managed to evolve in a way to bypass the signaling blockade or come up with a new way to maintain <a href="https://doi.org/10.1186/s12964-017-0173-2">proliferation</a>. Genes with increased activity are in metabolic pathways that allowed cancer cells to bypass BRAF altogether and continue to grow and divide. Cancer cells had essentially figured out how to survive by <a href="https://doi.org/10.1186/s40170-017-0168-x">rewiring their metabolism in response to chemotherapy</a>.</p>
<p><a href="https://doi.org/10.1186/s12918-018-0554-1">The research explains how tumors evolve and cause cancer resistance</a> to drugs designed to match the patient’s unique genomic makeup. Daunting as this may sound, it actually offers hope to scientists and clinicians who want to treat chemo-resistant cancers. The research brought forward valuable tools that will enable us to catch new forms of disease resistance before treatment regiments enter clinical trials.</p><img src="https://counter.theconversation.com/content/93633/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fabian V. Filipp, Assistant Professor of Systems Biology and Cancer Metabolism at the University of California Merced, receives funding from National Institutes of Health, National Cancer Institute, National Science Foundation, European Molecular Biology Organization, and the University of California Cancer Research Coordinating Committee. He is an elected council member of the PanAmerican Society for Pigment Cell Research.</span></em></p>Cancer is a disease of our genes, but resistance to therapy might go beyond cancer mutations. The DNA stays the same, but cancer cells outsmart the drugs by switching their gene activity.Fabian V. Filipp, Assistant Professor of Systems Biology and Cancer Metabolism, University of California, MercedLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/916082018-02-09T23:10:00Z2018-02-09T23:10:00ZCanada’s unsung female heroes of life sciences<figure><img src="https://images.theconversation.com/files/205770/original/file-20180209-51713-ighgwm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Former governor general David Johnston invests Toronto scientist Janet Rossant as a Companion of the Order of Canada during a ceremony at Rideau Hall in Ottawa in 2016. </span> <span class="attribution"><span class="source"> THE CANADIAN PRESS/Adrian Wyld</span></span></figcaption></figure><p><a href="http://www.un.org/en/events/women-and-girls-in-science-day/">International Day of Women and Girls in Science</a> is Feb. 11. To mark the occasion, let’s look back at some of Canada’s women life scientists. They’ve been pioneers in providing a foundation of knowledge through the sheer force of their world-class talent —going back more than a century. </p>
<p>Their legacy has established a knowledge foundation that represents the impact of real science. </p>
<p>Largely unknown by Canada’s decision-makers in government, industry and even the general public, their work is unheralded by ribbon-cutting ceremonies. Their relative obscurity in Canada, then and now, appears to be the preoccupation of how budgetary decisions are made as opposed to a consideration of talent and merit.</p>
<p>It’s high time to give them their due:</p>
<h2>Maud Menten</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/205763/original/file-20180209-51716-1jnuap1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/205763/original/file-20180209-51716-1jnuap1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=982&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205763/original/file-20180209-51716-1jnuap1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=982&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205763/original/file-20180209-51716-1jnuap1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=982&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205763/original/file-20180209-51716-1jnuap1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1234&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205763/original/file-20180209-51716-1jnuap1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1234&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205763/original/file-20180209-51716-1jnuap1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1234&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Maud Leonora Menten. Undated photo.</span>
<span class="attribution"><span class="source">(Smithsonian Institute)</span></span>
</figcaption>
</figure>
<p>At the turn of the century, University of Toronto medical graduate Maud Menten was barred from doing independent research in Canada as part of the accepted sexism of the day.</p>
<p>Her discovery in Berlin in 1913 provided the first insight into how chemical reactions in every cell of our body are regulated by enzymes. The discovery enabled enzymes to be purified, modified and targeted for drug therapy for disease. </p>
<p>Today enzymes serve as targets for about a third of all drugs in clinical use.
<br><br><br><br><br><br></p>
<h2>Maude Abbott</h2>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/205765/original/file-20180209-51697-oprili.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/205765/original/file-20180209-51697-oprili.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=851&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205765/original/file-20180209-51697-oprili.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=851&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205765/original/file-20180209-51697-oprili.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=851&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205765/original/file-20180209-51697-oprili.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1070&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205765/original/file-20180209-51697-oprili.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1070&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205765/original/file-20180209-51697-oprili.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1070&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Maude Abbott.</span>
<span class="attribution"><span class="source">McGill University</span></span>
</figcaption>
</figure>
<p>Maude Abbott was a world-renowned scholar, Bishop’s University medical graduate (1894) and a McGill University medical museum curator and pathology lecturer. </p>
<p>Her work in 1905 on congenital heart disease is critical to modern surgery. Abbott’s stunning pathology dissections are preserved today at the McGill Maude Abbott Medical Museum and remain unsurpassed to this day.
<br><br><br><br><br></p>
<h2>Brenda Milner</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/205766/original/file-20180209-51727-lj2w7b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/205766/original/file-20180209-51727-lj2w7b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205766/original/file-20180209-51727-lj2w7b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205766/original/file-20180209-51727-lj2w7b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205766/original/file-20180209-51727-lj2w7b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205766/original/file-20180209-51727-lj2w7b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205766/original/file-20180209-51727-lj2w7b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dr. Brenda Milner is seen in the House of Commons among other laureates of the Canadian Medical Hall of Fame in February 2002.</span>
<span class="attribution"><span class="source">(CP PHOTO/Jonathan Hayward)</span></span>
</figcaption>
</figure>
<p>In the middle of the 20th century, McGill’s Brenda Milner, a renowned scholar and founder of the field of neuropsychology, discovered that memory in humans is multiple and stored in several different parts of the brain. </p>
<p>Her discoveries in 1957 led to better treatments for a variety of brain disorders including trauma, degenerative and psychiatric diseases.</p>
<h2>Annette Herscovics</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/205768/original/file-20180209-51713-1yadvc9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/205768/original/file-20180209-51713-1yadvc9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=764&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205768/original/file-20180209-51713-1yadvc9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=764&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205768/original/file-20180209-51713-1yadvc9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=764&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205768/original/file-20180209-51713-1yadvc9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=960&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205768/original/file-20180209-51713-1yadvc9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=960&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205768/original/file-20180209-51713-1yadvc9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=960&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Annette Herscovics.</span>
<span class="attribution"><span class="source">McGill University</span></span>
</figcaption>
</figure>
<p>At McGill, Annette Herscovics discovered in 1969 that thyroglobulin, a precursor to thyroid hormone, undergoes carbohydrate modifications.</p>
<p>This was one of the first discoveries of a class of proteins known today as “glycoproteins.” Carbohydrate addition to proteins is today known as the most abundant protein modification for all life forms on the planet. </p>
<p>At Harvard in 1974, Herscovics then discovered the exact mechanism for carbohydrate addition that is a universal mechanism for all organisms with nucleated cells. </p>
<p>Upon returning to McGill in 1981, she discovered how these modifications are relevant to human disease, including cancer. </p>
<h2>Rose Johnstone</h2>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/205769/original/file-20180209-51703-f1d5bh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/205769/original/file-20180209-51703-f1d5bh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=870&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205769/original/file-20180209-51703-f1d5bh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=870&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205769/original/file-20180209-51703-f1d5bh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=870&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205769/original/file-20180209-51703-f1d5bh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1093&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205769/original/file-20180209-51703-f1d5bh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1093&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205769/original/file-20180209-51703-f1d5bh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1093&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Rose Johnstone.</span>
<span class="attribution"><span class="source">McGill University</span></span>
</figcaption>
</figure>
<p>Herscovics’s PhD supervisor was Rose Johnstone, who made a monumental discovery at McGill in 1983. </p>
<p>She discovered exactly how red blood cells in our body are made from precursor cells through a previously unknown structure she named “exosomes.” </p>
<p>Exosomes are now recognized as a universal protein delivery mechanism used by all cells in our body. They’re actively studied by academics and industry for the understanding and treatment of cancer, autoimmune diseases and neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease.</p>
<h2>Morag Park</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/205771/original/file-20180209-51723-28jrdl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/205771/original/file-20180209-51723-28jrdl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205771/original/file-20180209-51723-28jrdl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205771/original/file-20180209-51723-28jrdl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205771/original/file-20180209-51723-28jrdl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205771/original/file-20180209-51723-28jrdl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205771/original/file-20180209-51723-28jrdl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Morag Park.</span>
<span class="attribution"><span class="source">McGill University</span></span>
</figcaption>
</figure>
<p>At the U.S. National Cancer Institute in 1986, Morag Park’s work on mutant <a href="https://ghr.nlm.nih.gov/gene/MET">“MET” gene</a> association with several different cancers led to international prominence. </p>
<p>Today, Park is head of the McGill Cancer Research Centre, and has extended her discoveries to breast cancer and the importance of the surrounding normal cells in tumour progression.</p>
<h2>Janet Rossant</h2>
<p>Janet Rossant discovered the mechanisms used by embryos to generate organs and tissues with direct relevance to childhood diseases. </p>
<p>Her talent was first recognized at Brock University in 1977 and was followed by recruitment to the Lunenfeld Institute in Toronto. She was then director of the Research Institute of the Hospital for Sick Kids, and is now president and scientific director of the <a href="http://gairdner.org/">Gairdner Foundation.</a></p>
<h2>Mona Nemer</h2>
<p>Mona Nemer is currently Canada’s Chief Scientific Adviser discovered in Ottawa how genes that regulate the development of the heart help understand heart disease.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/205772/original/file-20180209-51719-1bd8ffd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/205772/original/file-20180209-51719-1bd8ffd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205772/original/file-20180209-51719-1bd8ffd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205772/original/file-20180209-51719-1bd8ffd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205772/original/file-20180209-51719-1bd8ffd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205772/original/file-20180209-51719-1bd8ffd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205772/original/file-20180209-51719-1bd8ffd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dr. Mona Nemer is introduced as Canada’s new Chief Science Advisor on Parliament Hill in September 2017.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Sean Kilpatrick</span></span>
</figcaption>
</figure>
<h2>Nada Jabado</h2>
<p>The discoveries of <a href="http://www.thechildren.com/departments-and-staff/staff/nada-jabado-md-phd-pediatric-hemato-oncologist">Nada Jabado</a>, a McGill physician scientist and paediatric cancer specialist, focus on how proteins are modified in cancer via the epigenome that mark the DNA in our genes to change the function of the gene. </p>
<h2>Heidi McBride</h2>
<p>McGill cell biologist <a href="http://mcbridelab.org/about/">Heidi McBride</a> has made transformative discoveries on the role of mitochondria (the energy factory in our cells) in cancer and neurological diseases, including Parkinson’s disease.</p>
<h2>Freda Miller</h2>
<p><a href="http://www.sickkids.ca/AboutSickKids/Directory/People/M/Freda-Miller.html">Freda Miller</a> at the Hospital for Sick Kids in Toronto has deciphered the mechanisms used to generate neuronal circuits during development from a thin sheet of non-neuronal precursor cells.</p>
<h2>Anne Claude Gingras</h2>
<p><a href="http://www.lunenfeld.ca/researchers/gingras">Anne Claude Gingras</a> of the Lunenfeld-Tanenbaum Research Institute in Toronto is a specialist in “quantitative proteomics.” It’s led to enormous advances in our understanding of cell organization with direct application to disease.</p>
<h2>Andrews, Arrowsmith and Edwards</h2>
<p>Brenda Andrews, Cheryl Arrowsmith, and Elizabeth Edwards are internationally renowned for their discoveries at the University of Toronto. </p>
<p><a href="http://sites.utoronto.ca/andrewslab/">Andrews</a> defines the new field of systems biology to understand cell organization using robots and Artificial Intelligence and its application to disease. </p>
<p><a href="http://nmr.uhnres.utoronto.ca/arrowsmith/">Arrowsmith’s</a> discoveries focus on cellular protein structure resolved at the atomic level to understand how chemical modifications regulate gene expression and their relevance to disease. </p>
<p><a href="http://www.chem-eng.utoronto.ca/faculty-staff/faculty-members/elizabeth-a-edwards/">Edwards’</a> work on “bioaugmentation” through anaerobic microbes to detoxify environmental pollutants is of direct relevance to the nightmare of toxic industrial and municipal waste accumulation.</p>
<h2>Impressive display of talent</h2>
<p>Taken together, these discoveries represent an impressive display of talent for real science that rivals scientists anywhere in the world.</p>
<p>Whatever country recognizes and establishes a genuine priority to enable real science by talented women scientists, and helps them thrive in discovery research, will be rewarded enormously. </p>
<p>Discovery research institutes such as the Crick Institute in the U.K. gather the most talented scientists, men and women, early in their careers, when discoveries are usually made. That assures a critical mass and merit-based value system that then provides the best of the discovery researchers to go out to populate universities, research institutes and industry. </p>
<p>A Canadian model could — and should —focus on women scientists, since they now may be Canada’s most talented. And also its most undervalued.</p>
<hr>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/91608/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Canada’s female scientists are superstars in their fields yet most Canadians have never heard of them. On International Day for Women in Science, it’s time to give them the recognition they deserve.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/908112018-02-01T15:54:20Z2018-02-01T15:54:20ZHow kindness can make a difference in cancer care<figure><img src="https://images.theconversation.com/files/204343/original/file-20180131-157491-28gwzb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In this Dec. 3, 2014 photo, liver cancer patient Crispin Lopez Serrano talks to an oncology nurse at a hospital in Clackamas, Ore.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Health-Overhaul-Palliative-Care/2239f6ec8a9d48328b642042787d1adc/32/0">AP Photo/Gosia Wozniacka</a></span></figcaption></figure><p>Cancer may not be life-ending, but it usually is life-changing. A cancer diagnosis instantaneously turns life upside down for patients and families. Cancer care is a <a href="https://hbr.org/2015/10/when-the-customer-is-stressed">“high-emotion” service</a>, and the care team must not only effectively treat the disease but also address patients’ intense emotions.</p>
<p>While accurate diagnosis and effective treatment are paramount, simple acts of kindness can be a potent antidote to negative emotions and may improve outcomes for those experiencing the frightening journey called cancer. A growing body of <a href="https://www.dignityhealth.org/about-us/press-center/press-releases/scientific-literature-review-with-stanford">evidence</a> reviewed at Stanford University shows that kind medical care can lead to faster wound healing, reduced pain, anxiety and blood pressure, and shorter hospital stays.</p>
<p>I have long studied how to improve service in health care. My current work focuses on cancer care and includes field research at 10 innovative U.S. cancer centers and interviews with approximately 400 cancer patients, family members, oncology clinicians and staff. Cancer care is about more than the science, which has led to important advances in treatment. High-touch needs to complement high-tech. In a recent <a href="http://ascopubs.org/doi/full/10.1200/JOP.2017.026195">paper</a>, co-authors and I explore how six types of kindness can improve cancer care.</p>
<p>Do we really need to remind caregivers about the importance of kindness in serving seriously ill patients? Unfortunately, yes, as the <a href="https://jamanetwork.com/journals/jama/fullarticle/2603408">stressors</a> of modern medicine often interfere with good intentions. Let’s take a quick look at the six types.</p>
<h2>Deep listening</h2>
<p>Listening intently to patients and families, with minimal interruption, conveys respect for their self-knowledge. It also builds trust. It enables the physician to act as a trusted guide who provides relevant medical expertise and translates it into a care plan consistent with patients’ values and priorities. The stakes are too high for the clinical team to be uninformed about a patient’s fears, practical concerns, home support system and personal <a href="https://hbr.org/2017/10/making-time-to-really-listen-to-your-patients?autocomplete=true">priorities</a>.</p>
<p>Genuine patient-centered care involves not only determining “what’s the matter” with the patient but also “<a href="http://www.nejm.org/doi/full/10.1056/NEJMp1109283">what matters to the patient</a>.” As a hospice nurse stated during my field research, “We cannot be afraid of the deep conversations with patients to find out what’s important to them, which you are not going to get by asking, ‘How are you feeling today?’”</p>
<p>Simple, open-ended questions can invite patients and families to share pertinent information. Intensive care unit nurses at Brigham and Women’s Hospital in Boston begin their shifts by asking patients, “<a href="http://ascopubs.org/doi/full/10.1200/JOP.2017.026195">What’s the most important thing we can do for you today?</a>”</p>
<h2>Empathy</h2>
<p>Nursing scholar <a href="http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2648.1996.12213.x/epdf">Theresa Wiseman</a> identifies four essential attributes of empathy: seeing the world from another’s perspective, avoiding judgment when assessing a situation, recognizing the emotion present, and responding to that emotion in a genuinely caring way. </p>
<p>One parent whose child was treated at Australia’s Peter MacCallum Radiation Center recounted, “My son had general anesthesia for radiation therapy. Because he was anxious about this procedure, the team allowed him to sit on me during anesthesia. When he woke up, he got upset about lacking a shirt. Now the team puts his shirt back on before he wakes … To me, these small acts were the ultimate kindness, reducing his anxiety and distress and, therefore, my own.”</p>
<p>Empathy represents an anticipatory kindness based on a caring assessment of the patient’s situation and likely stressors. At Henry Ford Hospital in Detroit, oncology fellows are trained in empathetic communication by improvisational actors who role play as patients and family members.</p>
<h2>Generous acts</h2>
<p>Kindness often manifests as generous acts. In my study, I asked patients, “Can you think of the best, most meaningful service experience you had as a cancer patient?” Many responses reflected the kindness embedded in generous acts. A bladder cancer patient who had undergone surgery praised a nurse who taught him the best way to get out of bed at home. Patients at Marin Cancer Care mentioned the foot massages they were offered during chemotherapy. A surgeon commented on a patient “who swears my two-minute hug saved her life.”</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/204344/original/file-20180131-157466-14mlplw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/204344/original/file-20180131-157466-14mlplw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=751&fit=crop&dpr=1 600w, https://images.theconversation.com/files/204344/original/file-20180131-157466-14mlplw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=751&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/204344/original/file-20180131-157466-14mlplw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=751&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/204344/original/file-20180131-157466-14mlplw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=943&fit=crop&dpr=1 754w, https://images.theconversation.com/files/204344/original/file-20180131-157466-14mlplw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=943&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/204344/original/file-20180131-157466-14mlplw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=943&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The author, Leonard Berry, stands by the seven binders of data he collected after studying three Wisconsin health systems.</span>
<span class="attribution"><span class="source">Leonard Berry/Author</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Generous acts also build employee pride and can offer a <a href="http://journals.sagepub.com/doi/full/10.1177/0001839214538636">renewing buffer</a> to the emotional fatigue and stress that commonly accompany caring for seriously ill patients.</p>
<h2>Timely care</h2>
<p>Undue waiting – for an appointment, the start of treatment or a consequential test result – can be excruciating for a cancer patient. An institutional commitment to being on time is kind even though delays are sometimes inevitable. As a cancer center administrator commented: “Every cancer center has a wait-time challenge; however, we can do much better on what we control, such as running our lab on time. Everyone must go through the lab. If the lab runs late, the whole thing goes late.”</p>
<p>Cancer centers can redesign their systems to deliver a bundle of getting started services to newly diagnosed patients within <a href="http://ascopubs.org/doi/full/10.1200/JOP.2016.011163">10 days</a>, establish a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482953/">multidisciplinary clinic day</a> when new patients meet each care team member to discuss the treatment plan, and open an urgent cancer care clinic to provide off-hours <a href="https://www.sciencedirect.com/science/article/pii/S2213076414000712?via%3Dihub">emergency service</a>. <a href="http://ascopubs.org/doi/full/10.1200/JOP.2016.017327">Telemedicine</a> and other technology-driven services also can minimize delays when time is of the essence.</p>
<h2>Gentle honesty</h2>
<p>“Cancer is a high-potency word, a word without any positive associations,” states a cancer patient. Asking patients how much they want to know about their illness is informative and kind. Most patients want to hear the <a href="https://jamanetwork.com/journals/jama/article-abstract/2466154?redirect=true">truth</a> in honest, well-chosen words that convey a sense of partnership and that guide them through difficult decisions.</p>
<p>An oncologist commented, “Far too often, patients and doctors are too optimistic. Realism is needed so that patients and their doctors can make good decisions.” A nurse practitioner said, “A doctor may say, ‘We can continue treatment or we can just do supportive care.’ We have to take the word ‘just’ out of that sentence.”</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/204345/original/file-20180201-157481-ihw3c3.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/204345/original/file-20180201-157481-ihw3c3.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/204345/original/file-20180201-157481-ihw3c3.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/204345/original/file-20180201-157481-ihw3c3.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/204345/original/file-20180201-157481-ihw3c3.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/204345/original/file-20180201-157481-ihw3c3.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/204345/original/file-20180201-157481-ihw3c3.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Leonard Berry, left, and Dr. Jonathan Leighton, a gastroenterologist at the Mayo Clinic, in Arizona, while Berry was working on a study there.</span>
<span class="attribution"><span class="source">Leonard Berry/Author</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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</figure>
<p>Oncologists face complex personal <a href="https://www.ncbi.nlm.nih.gov/labs/articles/10474749/">pressures</a> to give patients every chance to live, and they face external ones – from patients or family members who do not want to give up. </p>
<p>Although patients initially hope for cure or remission – focused hope – clinicians can guide them to <a href="http://blogs.bmj.com/bmj/2017/04/13/the-dual-nature-of-hope-at-the-end-of-life/">intrinsic hope</a> when the disease is advanced and cure or remission is improbable. Intrinsic hope involves living in the moment for a good day of positive reflection, a grandchild or a dog on one’s lap, and well-managed pain.</p>
<h2>Support for family caregivers</h2>
<p>Cancer patients commonly depend on family members for assistance with medical care, daily needs and emotional support. Family caregivers themselves require training, timely assistance and emotional care to perform their role and to maintain their own health. <a href="http://ascopubs.org/doi/full/10.1200/JCO.2011.39.5798">Research</a> shows the benefits of preparing, empowering and assisting a patient’s family to effectively care for a loved one. </p>
<p>The personal stories of patients, families and clinicians illustrate the impact of kindness in cancer care. Six overlapping manifestations of genuine kindness offer a powerful, practical way for clinicians to temper the emotional turmoil involved with a cancer diagnosis. </p>
<p>A patient is a person first. Caring for human needs as well as medical needs through kind acts is good medicine.</p><img src="https://counter.theconversation.com/content/90811/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Leonard L. Berry does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Great strides have been made in cancer medicine over decades, but it’s important not to forget the growing role that kindness and empathy play in good care.Leonard L. Berry, University Distinguished Professor of Marketing, Mays Business School; Senior Fellow, Institute for Healthcare Improvement, Texas A&M UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/880482017-12-05T10:09:18Z2017-12-05T10:09:18ZIt’s time to rethink how we do cancer research<figure><img src="https://images.theconversation.com/files/197343/original/file-20171201-17366-5vtw8e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Apple's Eyes Studio/Shutterstock.com</span></span></figcaption></figure><p>“<a href="https://www.theguardian.com/commentisfree/2017/oct/05/cancer-patients-survival-miracle-cures-medical-research">A devastating failure of medical research</a>.” This was the response of one cancer survivor on hearing the news that <a href="http://www.bmj.com/content/359/bmj.j4530?ijkey=09b39d8e242c6b801a1c36807974896d933fd707&keytype2=tf_ipsecsha">over half</a> of European Medical Agency-approved cancer treatments between 2009 and 2013 had no evidence of impact on quality of life or overall survival. As a cancer researcher, my goal above all is to improve patients’ lives – the fact we are failing at that struck me deeply.</p>
<p>Understandably, some people living with cancer are angry, feel betrayed, and are questioning why we do the research we do. Have cancer researchers lost sight of what is important in patient care? </p>
<p>Most anti-cancer treatments are first trialled in patients where cancer has already spread beyond a curable reach (the metastatic stage). This is because we feel we can’t offer an unproven treatment when others are available. Drug trials then tend to move to an earlier stage – take the example of <a href="http://news.bbc.co.uk/1/hi/health/5058952.stm">Herceptin</a>, which was developed to combat metastatic disease, but had such a huge impact it quickly moved to the curative early treatment stage. </p>
<p>This approach may seem to make sense, but right now, there is a bottleneck of treatments that have only limited benefit in delaying further spread of cancer in the metastatic stage. For many of these treatments, it is unlikely they will move to the curative stage as the benefits just don’t seem good enough. </p>
<p>Given all this, I think we need drastically to rethink our approach. </p>
<h2>Patients first</h2>
<p>We need to listen to what matters to patients. It is <a href="https://www.openaccessgovernment.org/highlighting-basic-research-cancer-treatment/22390/">often argued</a> that research needs space for blue sky thinking, the freedom to explore pathways and structures. But is there still room for that when we are confronted with the realities of increasing cancer rates, poor quality of life, with a 40-year-old with metastatic pancreatic cancer, for whom survival rates have <a href="https://www.sciencedaily.com/releases/2014/08/140807105106.htm">not improved</a> in the past four decades?</p>
<p>It is over ten years since the landmark <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360101/">MacMillan Listening Study</a> published its findings from in-depth consultations with groups of cancer patients and carers about their experiences. At that time, as now, the highest priority for patients was learning to live well with cancer. New treatments lagged significantly behind, coming in at number seven in patient’s priorities for cancer research. Yet fundraising campaigns still often focus on “finding a cure”. The emotional grab of a potential new anti-cancer treatment is seized on by reporters whereas the subtler improvements in quality of life are not. This means that funding for cancer research is skewed towards finding new treatments.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Patients need to be prioritised over research questions.</span>
<span class="attribution"><span class="source">Alexander Raths/Shutterstock.com</span></span>
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<p>We know early detection of cancer is key to improving survival ─ research in this area is not easy and doesn’t move quickly. Only this year has exclusive funding from Cancer Research UK <a href="http://www.cancerresearchuk.org/funding-for-reseachers/research-features/2017-06-19-new-funding-for-early-detection-research">been set aside</a> for early detection. But we need to encourage more research in this area. </p>
<p>Another area of chronic underfunding is <a href="http://stm.sciencemag.org/content/5/196/196cm6.full">biomarker research</a> – many currently available treatments don’t benefit everyone, but we don’t know how to select which individuals they do benefit. Making our existing treatments better rather than continuing to chase new treatments is often neglected.</p>
<p>We have seen some improvements in this area in recent years, particularly in the inclusion of patients and carers in developing cancer research. In my experience, these are motivated, caring individuals who are, more often than not, supportive of the research we do. But researchers need to be wary that we do not simply invite those whose voices we wish to hear – we must also include those who dissent with our views and challenge our research.</p>
<h2>Clinical trials</h2>
<p>Clinical trials tend to be designed around what we as researchers want to know, not always what patients need. I remember an impassioned plea for improved innovative trials from a woman who had lost her husband to melanoma. Even though they didn’t end up receiving the standard chemotherapy treatment (the control arm), her fear of her husband being selected for standard chemotherapy was so overwhelming it was now all she could remember. Can we focus our energy on making our trials better, switch up the design?</p>
<p>And of course, the trials are often funded by pharmaceutical companies, who want to show their drug in the best light. Today, many of our patients are too old for clinical trials, with the result that trials don’t necessarily reflect the real world of clinical treatment. In addition, several pharmaceutical companies can chase the same target, each hoping theirs is “the best”. This can saturate the market with “me too” drugs and stifle real innovation. The pharmaceutical industry has an important role to play, and they often play it well, of driving new treatments forward. But their need to keep an eye on the bottom line can be a distraction from the patient-centred research we need.</p>
<p>So what are some ways forward? We need a shift in research, away from a drug-focused approach to a more patient-focused approach, enshrining quality of life as a key outcome in clinical trials, ensuring we don’t accept inferior measurements of clinical benefit to approve a treatment. Most importantly, we need to value patients and carers as key partners in the progression of research. </p>
<p>By turning to those experiencing cancer treatment for the next big research questions and listening carefully to their answers, we can ensure those funding and performing research don’t get lost in a science maze, but have a clear view of the patient with every experiment.</p><img src="https://counter.theconversation.com/content/88048/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eileen Parkes receives funding from the Academy of Medical Sciences.</span></em></p>We need to ensure cancer research addresses what matters most.Eileen Parkes, Academic Clinical Lecturer, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/864352017-11-16T01:40:34Z2017-11-16T01:40:34ZThe two obstacles that are holding back Alzheimer’s research<figure><img src="https://images.theconversation.com/files/194821/original/file-20171115-19772-2rishs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Family members often become primary caregivers for loved ones with Alzheimer's disease. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/son-take-care-his-father-who-731853349?src=5DL3Iqb5un-9jop31gXxjQ-1-1">tonkid/Shutterstock.com</a></span></figcaption></figure><p>Thirty years ago, scientists began to unlock the mysteries regarding the <a href="https://www.alz.org/research/science/major_milestones_in_alzheimers.asp">cause of Alzheimer’s disease</a>. This knowledge ushered in an era of great enthusiasm that scientists could develop new therapies to either prevent Alzheimer’s or significantly slow the symptoms once present. </p>
<p>Despite continued progress and renewed hope that some therapies now in human trials will modify the course of the disease, the initial optimism of neuroscientists like me has been significantly tempered by reality. <a href="https://www.alz.org/research/science/major_milestones_in_alzheimers.asp">Numerous therapies</a>, most with sound scientific basis, have been tested and shown to be ineffective in humans with symptomatic Alzheimer’s disease.</p>
<p>Like the war on cancer, the war on Alzheimer’s disease is not going to be won in a single glorious “battle.” Instead, I believe incremental yet transformative progress will eventually lead to success. Unlike cancer, the scientific community does not yet have any “survivor stories” to buoy our efforts, and it will take a concerted effort by scientists, pharmaceutical companies, government and society to bring about the reality of ending Alzheimer’s disease. Only by recognizing and confronting all of the obstacles impeding development of Alzheimer’s therapies can we be confident that our battle will be successful. </p>
<p>As a physician-scientist and director of the University of Florida’s McKnight Brain Institute who began studying Alzheimer’s disease in medical school in the late 1980s, I appreciate the scope of the scientific advances we have collectively made. I have also come to the sobering realization that translating these advances into real therapies that will make a difference for patients suffering from this devastating disease is an incredibly complex issue which is not all about the science.</p>
<p>There are two significant, nonscientific obstacles – a shortage of funding and patent law – that will require concerted effort by scientists, concerned citizens, society and our lawmakers to overcome. </p>
<h2>Funding is improving, but still lagging</h2>
<p>Governments of industrialized nations have recognized research funding for Alzheimer’s disease and related dementias is insufficient. This lack of funding is drawing wider notice. Indeed, Bill Gates recently made a public recognition of the need for more funding and <a href="http://abcnews.go.com/Technology/wireStory/bill-gates-50-million-combat-alzheimers-51116689">pledged US$50 million</a> to Alzheimer’s research.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/194822/original/file-20171115-19841-4e4hks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/194822/original/file-20171115-19841-4e4hks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/194822/original/file-20171115-19841-4e4hks.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/194822/original/file-20171115-19841-4e4hks.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/194822/original/file-20171115-19841-4e4hks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/194822/original/file-20171115-19841-4e4hks.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/194822/original/file-20171115-19841-4e4hks.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Bill Gates in a Feb. 22, 2016 photo taken in New York City.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Gates-Alzheimer-s-Donation/72587125f2e3414f8197abe0806101f9/1/0">AP Photo/Seth Wenig</a></span>
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<p>Just within the U.S., National Institute of Health funding has increased in the past five years from <a href="https://www.aging.senate.gov/press-releases/senator-collins-applauds-new-national-academies-of-sciences-report-on-preventing-cognitive-decline-and-dementia">$503 million per year to $1.391 billion</a> per year, and an increase of an additional <a href="https://alzheimersnewstoday.com/2017/05/09/alzheimers-groups-welcome-40-increase-nih-research-funds-authorized-congress/">some $400 million</a> is being proposed for 2018.</p>
<p>To many, even $500 million per year may sound like a lot of funds, but given current costs to U.S. society of about <a href="http://act.alz.org/site/DocServer/2012_Costs_Fact_Sheet_version_2.pdf?docID=7161">$200-$250 billion per year</a> from Alzheimer’s, money spent on research is a drop in the bucket. Furthermore, compared to funding on cancer (<a href="https://www.cancer.gov/about-nci/budget">about $6 billion</a> per year from the NIH), I believe this additional funding is both appropriate and necessary.</p>
<p>Due to increasing number of Americans living longer lives, Alzheimer’s advocacy groups and others estimate that the number of individuals suffering from dementia may almost <a href="https://www.alz.org/documents_custom/trajectory.pdf">triple, from 5 million</a> to 13.5 million.</p>
<p>We are on the right track, but if we can spend $6 billion per year on cancer, we may need to spend that much on dementia to make a difference. </p>
<h2>Prevention an important but unrealized goal</h2>
<p>One of the challenges in treating the disease is that the brain is riddled with pathology by the time a person shows symptoms of Alzheimer’s. Many research efforts are therefore looking at prevention.</p>
<p>We now know that the pathologies driving the disease – protein deposits called amyloid plaques and neurofibrillay tangles – appear about 20 or more years before overt symptoms of dementia appear. </p>
<p>These gradually accumulate sequentially in the brain, with amyloid preceding abnormal tangle pathology, and tangle pathology seemingly more tightly linked to cognitive decline. </p>
<p>Thus, if we can prevent these deposits with small-molecule drugs, antibodies or even gene therapies, we might prevent Alzheimer’s disease. A number of studies are underway, but no preventative therapies exist.</p>
<p>Though lifestyle interventions such as exercise and “memory-enhancing” mind games are also being investigated as possible ways to stave off or slow down cognitive decline, there is no evidence that these actually alter the underlying pathology and little evidence that they slow the disease course. </p>
<p>I have seen too many people who lived the healthiest lifestyle and stayed intellectually and socially active throughout their lives, yet still developed Alzheimer’s. They are testament to why we need therapies that actually alter the pathobiological process underlying the disease. </p>
<h2>A surprise impediment: Patent law</h2>
<p>A major, largely unspoken block to testing and developing the best therapies for prevention is the current patent law. </p>
<p><a href="https://www.scientificamerican.com/article/cost-to-develop-new-pharmaceutical-drug-now-exceeds-2-5b/">Costs of running definitive clinical trials</a> necessary to test even a symptomatic therapy can exceed $1 billion, and the costs of prevention trials will far exceed that figure. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/194825/original/file-20171115-19836-95yxyp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/194825/original/file-20171115-19836-95yxyp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/194825/original/file-20171115-19836-95yxyp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/194825/original/file-20171115-19836-95yxyp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/194825/original/file-20171115-19836-95yxyp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/194825/original/file-20171115-19836-95yxyp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/194825/original/file-20171115-19836-95yxyp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Clinical trials can take years to complete.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/scientist-laboratory-628397483?src=ucKh9_BWdwnruOwyiVY-Dg-1-8">Atellier211/shutterstock.com</a></span>
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<p>Prevention trials are likely to take five to 10 – or more – years before they yield an answer as to whether the drug or intervention is working. Patent protection and market exclusivity may already have expired by the time a drug is approved or have only a few years remaining. </p>
<p>This severely limits the ability for the pharmaceutical sector to invest in Alzheimer’s prevention studies: They cannot justify the cost from a business point of view. </p>
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<figcaption><span class="caption">Dr. Todd Golde, director of the McKnight Brain Institute at the University of Florida, discusses Alzheimer’s research.</span></figcaption>
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<p>This presents a huge dilemma. Researchers, and those we hope to help, need private-sector investment, but the private sector does not have a clear financial incentive to conduct these studies. Scientists in pharmaceutical companies simply cannot make the business case for risking billions of dollars to develop and test Alzheimer’s prevention therapy that may or may not work, if it would be approved for use only after the patent protecting the therapy has expired. The company would never be able to recoup the development costs. </p>
<p>That’s why our society needs a new financial model for developing preventive therapies that encourage the long-term risky investments required. One model that could be considered would be for regulators to permit market exclusivity even without patent protection for a period of time that enables the company to make a typical return on investment for a “blockbuster” therapy. This could be negotiated on a case-by-case basis with a prespecified formula for the ROI.</p>
<h2>Toward a brighter future</h2>
<p>Even as we move toward prevention of Alzheimer’s, researchers recognize that we must continue efforts to help those currently suffering from the disease and those likely get the disease before we develop effective preventative measures.</p>
<p>As a field, researchers are learning from our past failures. Our knowledge of the disease is inexorably increasing, and our tools have never been better. </p>
<p>Moreover, the increased funding is attracting new researchers with new ideas that could potentially be the game changers. Because of these advances, I remain optimistic that not only will we prevent Alzheimer’s but we will be able to make a difference for those who will get the disease in the near future. Indeed, working together, we hope to change the lexicon around Alzheimer’s and related dementias from inevitable and untreatable to preventable and treatable.</p><img src="https://counter.theconversation.com/content/86435/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr. Todd Golde receives funding from the NIH (P01CA166009, U011AG046139, R01AG018454, P50AG047266, R21NS102926) . He is a cofounder of Lacerta Inc. He holds stock options and is a scientific advisor to Promis therapeutics. He has consulted for Abbvie and ELi Lilly in the past two years and has received funds for travel and speaking at Roche. He is a full time employee of the University of Florida, where he directs the McKnight Brain Institute, is a Professor of Neuroscience in Uf's College of Medicine. </span></em></p>The first clinical trial examining a drug to treat Alzheimer’s was begun 30 years ago. There is still no cure and no known way to prevent the disease. Two factors may contribute to that.Todd Golde, Director, Evelyn F. and William L. McKnight Brain Institute Director, 1Florida Alzheimer’s Disease Research Center, Professor, Department of Neuroscience, College of Medicine University of Florida, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/719472017-01-31T15:52:58Z2017-01-31T15:52:58ZHow the landscape has changed in the search for a cure for breast cancer<figure><img src="https://images.theconversation.com/files/154957/original/image-20170131-13238-b00n65.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Advances in breast cancer research in the last decade has introduced new treatment regimes.</span> </figcaption></figure><p>Today nearly every women’s magazine carries articles on breast cancer. The month of <a href="http://www.who.int/cancer/events/breast_cancer_month/en/">October</a> – as the official breast cancer awareness month – brings thousands of people together for breast cancer walks, races, pink ribbon awareness luncheons, and educational seminars, all targeting the disease. </p>
<p>The goal is always to raise funds for <a href="https://www.bcrfcure.org/">research</a> and for better treatments and an eventual cure.</p>
<p>When I’m feeling down because a patient I have become close to has succumbed to this disease, I only need to visit the breast cancer Research Labs at <a href="http://www.hopkinsmedicine.org/research/centers.html">Johns Hopkins </a> in Baltimore in the US to feel hopeful for future patients.</p>
<p>I have been involved in cancer research for the last 12 years, specifically looking at <a href="https://www.researchgate.net/profile/Ronald_Wasike/citations?sorting=citationCount&page=1">advances in breast cancer treatment</a>. I have recently published a book – Breast cancer: what we all need to know – which is aimed at people diagnosed with breast cancer as part of an effort to help them and their families cope better.</p>
<p>Great <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860343/">progress</a> has been made in the fight against breast cancer over the last three decades. It’s important not to lose sight of these. </p>
<h2>Major developments</h2>
<p>There have been breakthroughs ranging from the diagnosis to the treatment including <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa020989#t=article">new surgical techniques</a> and drug combinations in the management of breast cancer in the last two decades.</p>
<p>These include</p>
<ul>
<li><p>Targeted therapy is being developed to increase survival odds for women with aggressive, difficult to <a href="http://www.breastcancer.org/treatment/targeted_therapies">control tumours</a>. These therapies block the growth and spread of cancer by interfering with specific molecules that encourage the growth and spread of the cancer.</p></li>
<li><p>Genetic testing is being made available for <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet">breast cancer genes</a> that predispose an individual to getting the disease. About 5% to 10% of the breast cancer in some women is due to changes in the structure of a number of genes that may run in <a href="http://ww5.komen.org/BreastCancer/GeneMutationsampGeneticTesting.html">generations of families</a> . This means that women from families where breast cancer has been diagnosed can be tested and preventive measures can be taken.</p></li>
<li><p>More clinical trials have been developed and completed showing benefits of specific chemotherapy agents and what combinations could be more <a href="http://ww5.komen.org/BreastCancer/TheChemotherapyDrugs.html">useful</a>. When drugs are developed and tested in laboratories and animals, the next stage is to test them on people with the disease under well controlled environment to gauge their efficacy and side effects before they are released.</p></li>
<li><p>Shortened radiation therapy <a href="https://www.ncbi.nlm.nih.gov/pubmed/24479632">techniques</a> have been developed. Instead of patients being placed under an external beam of radiation for 20 to 30 days, rods, beads or small balls containing radiation materials are inserted in the operation site for a few hours or days. This is done during operation for breast or prostate cancer.</p></li>
</ul>
<p>These are only a partial list of breakthroughs that have happened in a little more than a decade.</p>
<h2>More research underway</h2>
<p>In addition to these breakthroughs there are other treatments that are in their clinical trial stages. These include:</p>
<ul>
<li><p>Newer chemotherapy combinations that promise to improve breast cancer survival. They include newly developed anti cancer drugs that <a href="http://www.webmd.com/breast-cancer/features/new-treatments-for-breast-cancer">prevent tumour cells </a> from dividing further.</p></li>
<li><p>Breast <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192521/">conservation surgery</a> : previously a decision would have been made to remove a woman’s breast if she had a big tumour. But the aim is increasingly to remove the tumour without removing the breast. In addition, it’s often better to treat a patient with chemotherapy first to target possible circulating cancer cells and to help shrink the tumour before surgery.</p></li>
<li><p>The administration of chemotherapy directly into the ducts of the breast to destroy the source of the disease, and </p></li>
<li><p>a range of new hormonal therapies and vaccine therapies that are being tested.</p></li>
</ul>
<h2>A cure in our lifetime</h2>
<p>We are developing a better understanding of why and how breast cancer spreads recognising that if we could prevent it from ever spreading, frankly, no one would die of this disease.</p>
<p>In laboratories, petri dishes breast cancer cells are being studied to further understand what stimulates them to grow and thrive. There’s also exciting research looking at ways to prevent breast tissue from ever allowing cells to mutate into a breast cancer cell.</p>
<p>I am confident that in our lifetime we will have the opportunity to see this disease listed in medical books in the chapter under “cured diseases” where polio is listed today. Until then, I’ll be looking for you at future breast cancer events, proudly wearing your pink hat or T-shirt proclaiming that you are a breast cancer survivor.</p>
<p><em>This is an edited version of a chapter in the book Breast cancer: what we all need to know by Professor Ronald Wasike.</em></p><img src="https://counter.theconversation.com/content/71947/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ronald Wasike does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The chances of surviving breast cancer are improving everyday due to advanced research and new treatment techniques.Ronald Wasike, Professor & Consultant Breast Surgeon, Aga Khan University Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/661252016-10-03T19:16:27Z2016-10-03T19:16:27ZWomen should be told about their breast density when they have a mammogram<figure><img src="https://images.theconversation.com/files/139540/original/image-20160928-736-273r8y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Breast density appears white or bright on mammograms – so do breast cancers. </span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-196939097/stock-photo-x-ray-mammogram-image-of-breast-with-cancer.html?src=pp-same_artist-196939100-1&ws=1">Tomas K/Shutterstock</a></span></figcaption></figure><p>Women with higher breast density for their age are more likely to develop breast cancer. High breast density also makes it harder for doctors to detect breast cancer on a mammogram. But Australian women are not routinely tested for and told about their level of breast density when they undergo a mammogram. </p>
<p>A woman’s breasts are made up of dense breast tissue and fatty breast tissue. Almost <a href="http://jnci.oxfordjournals.org/content/106/10/dju255.short">8% of women aged between 40 and 74 years</a> have extremely high breast density. This means they have more connective tissue and less fat surrounding their glands. </p>
<p>Breast density can’t be determined just from looking at or physically examining the breasts; it’s measured from a mammogram, an X-ray of the breast. Breast density appears white or bright, while non-dense breast tissue appears dark.</p>
<p>Breast cancers also appear white on a mammogram. So having high breast density can mask or hide the cancer, making early detection more difficult. This is especially important because women whose breast cancers that are found within 24 months of a “clear” mammogram tend to have poorer outcomes.</p>
<p>Across the population, a woman has a 12.5% chance of getting breast cancer in her lifetime. Women who have high breast density for their age and body mass index (BMI) have a <a href="https://www.ncbi.nlm.nih.gov/pubmed/16775176">four to six-times higher</a> risk of developing breast cancer in the future compared to women with low breast density. </p>
<p>We are a group of breast cancer scientists concerned that Australian women are not being made aware of the significance of breast density in the diagnosis and prevention of breast cancer. We want to start a conversation about what density is, even though we don’t yet have all the answers.</p>
<p>We would like to see health professionals (including researchers, radiologists, GPs and BreastScreen) begin talking with women about the best way to measure and report breast density. </p>
<h2>What can women do about it?</h2>
<p>A woman’s breast density is established at the time her breasts form, and is largely determined by genetic factors. </p>
<p>“Environmental” factors then can modify breast density over time. This includes having children, which reduces breast density, and taking certain hormone therapies: hormone replacement therapy increases density, while the drug <a href="https://www.ncbi.nlm.nih.gov/pubmed/21483019">Tamoxifen</a> decreases density.</p>
<hr>
<blockquote>
<p><strong>Further reading:</strong> <a href="https://theconversation.com/how-does-breast-density-impact-on-cancer-screening-34700">How does breast density impact on cancer screening?</a></p>
</blockquote>
<hr>
<p>We don’t yet have a straightforward answer about what women with high breast density for their age should do. </p>
<p>Being “breast aware” is important for all women, but particularly women with higher breast density. Get to know how your breasts feel and check them regularly for changes. </p>
<p>Mammography is the best breast cancer screening test for women aged 50-74 who aren’t showing any symptoms. Early detection improves the outcomes for women with breast cancer, as therapies are more effective at early stages of disease and chances of survival are increased. </p>
<p>For women aged 40 to 49 and over 75, the research is less clear about the benefits of breast screening. </p>
<p>Supplemental screening options such as ultrasound and MRI (magnetic resonance imaging) are available for women with high breast density. However, these also have a number of limitations and are not covered by Medicare for this purpose. </p>
<p>Ultrasound often results in high rates of false positives, indicating that breast cancer is present when it is not. A false positive can be a distressing experience, with additional tests sometimes being required such as a breast biopsy. </p>
<p>MRI does not lead to higher false positives, but it is not a feasible option for a population-based screening program because of the high costs and insufficient MRI resources (equipment and trained staff). </p>
<p>A further problem is there are few options to reduce breast density once it is detected. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/21483019">Tamoxifen</a> is a drug used to prevent or treat breast cancer that reduces breast density and breast cancer risk. But it has significant side effects such as hot flashes, vaginal dryness, low libido, mood swings and nausea, which need to be considered on a patient-by-patient basis. </p>
<p>In counselling women about their breast cancer risk and screening options, clinicians will also ask about a women’s other breast cancer risk factors, particularly family history of the disease.</p>
<h2>What might be available in future?</h2>
<p>Researchers and clinicians have been investigating breast density for around 40 years. But there is still a lot we do not know. </p>
<p>The long-term goal of our research – in Australia and abroad – is a tailored screening program where women undergo good-quality screening measures based on their levels of breast density and their breast cancer risk. </p>
<p>First, we need to determine if women with higher breast density would benefit from supplemental screening mentioned above, or annual mammograms. </p>
<p>Our research teams are currently investigating:</p>
<ul>
<li><p>the underlying biology of breast density to inform the development of new drugs to decrease density </p></li>
<li><p>the optimal methods of measuring breast density across the population and in younger women, for whom mammography is not recommended</p></li>
<li><p><a href="http://www.lifepool.org/">breast cancer risk prediction models</a> to determine the individual likelihood of developing the disease or having it go undetected </p></li>
<li><p>breast density in <a href="http://crowdresearch.uwa.edu.au/project/are-your-breasts-dense/">Aboriginal women and younger women</a></p></li>
<li><p>and the genetic determinants of breast density and breast cancer risk to inform individual risk prediction models.</p></li>
</ul>
<p>We don’t want to scare women that have higher breast density for their age. Rather, we want to inform them about their risk of breast cancer and the additional care they should take until we find treatments that can reduce density and breast cancer risk. Not all women with high breast density will develop breast cancer, but they should be aware that they are at an increased risk.</p>
<hr>
<p><em>For more information on breast density, visit the <a href="http://www.informd.org.au">INFORMD website</a>.</em></p><img src="https://counter.theconversation.com/content/66125/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kara Britt receives funding from National Breast Cancer Research Foundation of Australia and the Peter MacCallum Cancer Research Centre. She is a member of INFORMD (Information FORum on Mammographic Density), an Australian alliance of breast cancer researchers who aim to increase awareness of the importance of breast density in screening, diagnosis and prevention of breast cancer.</span></em></p><p class="fine-print"><em><span>Honor Joy Hugo has received funding from the National Breast Cancer Foundation, Victorian Cancer Agency and is currently funded by a Translational Research Institute SPORE grant and a National Breast Cancer Foundation collaborative research grant called EMPathy. She is a member of INFORMD.
</span></em></p><p class="fine-print"><em><span>Jennifer Stone received grant funding to conduct breast density research from The National Breast Cancer Foundation, Cancer Australia, Cancer Council Western Australia, Cancer Council Victoria, National Health & Medical Research Council, Royal Perth Hospital Medical Research Foundation, Breast Cancer Research Centre Western Australia, Victoria Cancer Agency, and the Victorian Breast Cancer Research Consortium. She is a member of INFORMD.</span></em></p><p class="fine-print"><em><span>John Hopper receives funding from the NHMRC, Cancer Australia, the National Breast Cancer Foundation, the National Institutes of Health and Cancer Council Victoria. He is a member of INFORMD. </span></em></p><p class="fine-print"><em><span>Pallave Dasari receives funding from The Hospital Research Foundation. She is a member of INFORMD.</span></em></p><p class="fine-print"><em><span>Rik Thompson has received funding from the St Vincent's Hospital Research Endowment Fund, the Princess Alexandra Hospital Foundation, the Victorian Breast Cancer Research Consortium and the Translational Research Institute. He is a member of INFORMD.</span></em></p><p class="fine-print"><em><span>Wendy Ingman receives funding from the National Health and Medical Research Council, the National Breast Cancer Foundation and The Hospital Research Foundation. She is a member of INFORMD.</span></em></p>Women with dense breasts are more likely to develop breast cancer. Density also makes it harder for doctors to detect breast cancer on a mammogram.Kara Britt, Senior Research Fellow at Peter MacCallum Cancer Centre; Adjunct Lecturer, Monash UniversityHonor Joy Hugo, Postdoctoral Research Fellow, Queensland University of TechnologyJennifer Stone, Senior Research Fellow, Centre for Genetic Origins of Health and Disease, The University of Western AustraliaJohn Hopper, NHMRC Australia Fellow, The University of MelbournePallave Dasari, Australian Breast Cancer Research Postdoctoral Fellow, The Queen Elizabeth Hospital and The Robinson Institute, University of AdelaideRik Thompson, Professor of Breast Cancer Research, Institute of Health and Biomedical Innovation and School of Biomedical Sciences,, Queensland University of TechnologyWendy Ingman, Associate Professor, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/613762016-06-29T19:46:12Z2016-06-29T19:46:12ZGlioblastoma: why these brain cancers are so difficult to treat<figure><img src="https://images.theconversation.com/files/128011/original/image-20160624-28366-1lzm508.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Glioblastomas are often resistant to the one type of drug that breaks the blood-brain barrier.</span> <span class="attribution"><a class="source" href="http://healthhub.brighamandwomens.org/five-things-you-need-to-know-about-glioblastomas#sthash.Gjm7LSGW.vq7cd4lH.dpbs">HealthHub</a></span></figcaption></figure><p>You find yourself sitting in your doctor’s surgery. It’s only been a few days since your initial visit to check on these pounding headaches you’ve been waking up with, along with some dizziness, nausea and vomiting, and a general drowsy and disconnected feeling. </p>
<p>You thought it was a flu or other common virus, but the doctor has run a few tests, including an MRI. Then your world collapses as you’re told you have a brain tumour. A biopsy would have to be taken, but if this shows it’s glioblastoma multiforme (or commonly just called glioblastoma) you may only have as little as a few months to live.</p>
<p>This is the scenario faced by the around one thousand Australians diagnosed with glioblastoma each year. </p>
<p>While it is important to note the symptoms outlined above can occur for a variety of other reasons, they commonly occur in glioblastoma patients, who, depending on the location of the tumour in the brain, may also have a range of other symptoms, including weakness on one side of the body, memory and speech difficulties, and changes in vision.</p>
<p>Glioblastoma can affect any age group, but is more common in older people (average age of diagnosis is 64), and for reasons that are not clear, is somewhat more common in males. </p>
<p>The exact cause of glioblastoma is not known. The tumour arises from astrocytes, cells named because of their star shape, that make up the supportive tissue of the brain. These tumours usually grow very fast, and can easily invade surrounding normal brain tissue, making it a particularly aggressive form of cancer where treatment success is still very limited.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=446&fit=crop&dpr=1 600w, https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=446&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=446&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=561&fit=crop&dpr=1 754w, https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=561&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/128436/original/image-20160628-28373-45jfwj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=561&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">These tumours grow from astrocytes - the cells that make up the supportive tissue in the brain.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
</figcaption>
</figure>
<p>Treatment for glioblastoma normally involves surgical removal of the bulk of the tumour, followed by radiation and chemotherapy with a drug called temozolomide. </p>
<p>Even with this treatment, however, the prognosis for glioblastoma patients is bleak, with only half the patients surviving for 15 months, with less than 5% of patients still alive five years after diagnosis. These are particularly sobering statistics, much worse than other common cancers. </p>
<h2>Why is glioblastoma so hard to treat?</h2>
<p>Surgical removal of the entire tumour is almost impossible, and in most cases less than 90% can be removed. Glioblastoma is often referred to as having finger-like tentacles that extend some distance from the main tumour mass into surrounding normal brain tissue. </p>
<p>Unlike tumours in other parts of the body where a clear margin of normal tissue surrounding the tumour can often be taken to maximise the chances of complete tumour removal, this is generally not feasible for the brain where a balance has to be made between tumour removal and risks to cognitive function, or indeed immediate patient survival. </p>
<p>So some tumour is inevitably left and can reform in the initial tumour site or in other areas of the brain.</p>
<p>Another reason they are so tough to treat is that many drugs cannot efficiently enter the brain to act on the tumour. There is a unique barrier, termed the “blood-brain barrier” that limits the passage of molecules, like many chemo drugs, from the bloodstream into the brain. </p>
<p>Many drugs that may block glioblastoma growth in the lab simply do not work effectively in patients because of this barrier. The chemotherapy drug temozolomide does cross the blood-brain barrier, which is a major reason for its clinical use for this cancer.</p>
<p>However glioblastoma cells are often resistant to temozolomide. Many glioblastomas produce a protein (called MGMT) which can limit the effects of temozolomide. The presence of MGMT can be a good indication of whether a patient will respond to chemo drugs, and thus how long they will survive.</p>
<p>Many solid tumours presenting in other parts of the body can often grow very large without immediate impact on the patient. The physical location of glioblastoma within the confined space of the skull, and surrounded by vital normal brain tissue, however, means that even small increases in tumour size can have serious effects on cognitive function or patient survival. This is why effective therapy has to happen quickly, with little margin for error. </p>
<p>The challenge remains for researchers and doctors to develop better therapies for this devastating disease. Numerous <a href="http://www.clinicaltrials.gov/">pre-clinical studies and clinical trials</a> are currently in progress, exploring multiple avenues to tackle this cancer, such as better temozolomide-like drugs, targeted therapies aimed at the defective genes thought to drive glioblastoma development, tumour-killing viruses, or immunotherapies harnessing the body’s own immune system to target the cancer.</p>
<p>Some of these approaches show considerable promise, providing hope for the future.</p><img src="https://counter.theconversation.com/content/61376/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stuart Pitson receives funding from the Neurosurgical Research Foundation and the National Health and Medical Research Council of Australia. </span></em></p>Glioblastoma is an aggressive form of brain cancer that has a very poor prognosis. Despite the current best therapies half its sufferers survive for 15 months and less than 5% are alive after 5 years.Stuart Pitson, NHMRC Senior Research Fellow, Centre for Cancer Biology, University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/363442015-02-02T19:04:04Z2015-02-02T19:04:04ZSpot the snake oil: telling good cancer research from bad<figure><img src="https://images.theconversation.com/files/70802/original/image-20150202-13074-1krqyx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There are ways non-scientists can assess if the research underlying big claims about cancer cures stacks up.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/andercismo/2349098787">Rafael Anderson Gonzales Mendoza/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p>Cancer is big news; we often hear of some kind of cure for some version of the illness. But whether it’s a “natural cure” or a promising molecule on its way to becoming a new medicine, there are ways non-scientists can assess if the research underlying the big claims stacks up.</p>
<p>Here are some tips to help you evaluate whether a cure claim is justifiable (spoiler: the evidence is rarely robust enough).</p>
<h2>Cell line testing</h2>
<p>As a minimum, any cure claim needs to demonstrate that the new molecule or natural therapy can stop the growth of cancer cells in what you might think of as test-tube experiments. Scientists call these <em>in vitro</em> tests (Latin for “in glass”).</p>
<p>These types of tests are the first in a long line because they’re cheap, easy, don’t require ethics approval and can be completed in one or two days. </p>
<p>The most important thing to look for in the results is whether an approved drug is used for comparison. The new cure needs to stop cancer growth at a dose lower than the comparison drug. And it needs to stop cancer cell growth at doses ten to 100 times lower than the approved drug to be really exciting.</p>
<p>Unfortunately, it’s very easy to get a good result in these kinds of tests and many hundreds of drugs are found to be just as effective as approved drugs. If curing cancer was simply a matter of getting a pass at this point, then we would indeed have cured it ten of thousands of times over. </p>
<p>Much of the evidence cited by non-scientists for natural cure claims are based solely on these <em>in vitro</em> tests. In reality, these experiments are only used as a screening (stop-or-go) test to determine whether the next level of testing is justified.</p>
<h2>Animal testing</h2>
<p>The next level is animal testing – and by animal, 99% of the time we mean <a href="http://www.medicinenet.com/script/main/art.asp?articlekey=33771">specially bred mice</a>. Animal experiments are known as <em>in vivo</em> tests (Latin for “within the living”). </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/70800/original/image-20150202-13049-14hw3w6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/70800/original/image-20150202-13049-14hw3w6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=426&fit=crop&dpr=1 600w, https://images.theconversation.com/files/70800/original/image-20150202-13049-14hw3w6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=426&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/70800/original/image-20150202-13049-14hw3w6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=426&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/70800/original/image-20150202-13049-14hw3w6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=536&fit=crop&dpr=1 754w, https://images.theconversation.com/files/70800/original/image-20150202-13049-14hw3w6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=536&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/70800/original/image-20150202-13049-14hw3w6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=536&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Specially bred mice, called nude mice, are usually used for <em>in vivo</em> tests.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/parksdh/15201585979">Daniel Parks</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>So what do you look for here? First, beware of tests that use more exotic or less established animal models, such as <a href="http://www.microtestlabs.com/zebrafish-embryos-testing/">zebra fish embryos</a> as the correlation of the results in these animals to humans is less certain. </p>
<p>And, again, make sure it has been compared to an approved drug, and that the drug is used in humans to treat the type of cancer the tested animal had. Experiments that use the incorrect drug for the cancer they are testing against will make the “cure” look better.</p>
<p>Look out for how often the animals are given the treatment. Most tests use a single treatment early in the study, but some use a schedule of multiple treatments. There can be valid reasons for using multiple treatments, but more treatments do make it a positive result more likely. </p>
<p>Also look out for <em>in vivo</em> tests where the approved drug is given one way (like an injection) but the new drug is given a different way (swallowed or inhaled). It’s hard to compare them accurately in these circumstances.</p>
<p>Next, look for how well it delays cancer growth compared with the approved drug. Is the difference only small or is the delay quite evident? Have the scientists shown a <a href="https://www.statpac.com/surveys/statistical-significance.htm">statistical difference</a> in cancer growth (they’ll mention this somewhere in the research paper) under the two treatment regimes? </p>
<p>Remember, these tests are just another stop-or-go checkpoint to warrant further testing. By themselves, they don’t indicate the new cure will work for humans. And many that do work in these tests go on to have no effectiveness in people.</p>
<h2>Clinical trials</h2>
<p><a href="http://medicinesaustralia.com.au/issues-information/clinical-trials/">Clinical trials</a> are really the point where you can start to pay attention to cure claims. This is when the first testing on humans takes place. But not all clinical trials are created equal. </p>
<p>There are three main levels. Phase I is only for determining side effects and effectiveness is not of primary concern. But it’s not uncommon for one or two patients to have cancers that respond to treatment. A positive result at this stage doesn’t indicate it will work for all patients, so beware of any study that claims a cure based only on phase I tests.</p>
<p>Phase II and phase III trials, where the drug is tested in specific cancer types and compared alongside approved drugs, are the important ones.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/70804/original/image-20150202-13057-13uyo9n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/70804/original/image-20150202-13057-13uyo9n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/70804/original/image-20150202-13057-13uyo9n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/70804/original/image-20150202-13057-13uyo9n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/70804/original/image-20150202-13057-13uyo9n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/70804/original/image-20150202-13057-13uyo9n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/70804/original/image-20150202-13057-13uyo9n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The key for understanding the results of many of the tests is ensuring the right things are compared.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/picturesofthings/2395065912">nikki/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>The key thing to look for in the results is the overall survival rate (how many patients live for five years after the start of treatment) or the improvement in time-to-disease progression (the amount of time from the start of treatment until the cancer spreads or gets bigger). </p>
<p>Phase II, and more importantly phase III, trials are highly regulated. Any positive results claimed in the findings are reliable and indicative of real potential to make a difference in cancer treatment.</p>
<p>You can find details of cancer clinical trials in Australia <a href="http://www.australiancancertrials.gov.au/">here</a>, in the United States <a href="https://www.clinicaltrials.gov/">here</a> and in the European Union <a href="https://www.clinicaltrialsregister.eu/ctr-search/search">here</a>.</p>
<h2>Anecdotes are not evidence</h2>
<p>There’s a saying among scientists, “the plural of anecdote is not data”. And you’ve undoubtedly heard one of a hundred stories of how John or Jane Smith down the street was cured when treated with oil-of-something. </p>
<p>Many possible explanations for such “cures” may have nothing to do with their miracle substance. First, there could be a strong <a href="https://theconversation.com/to-understand-placebo-first-take-it-out-of-medicines-black-box-11004">placebo effect</a>; just the belief that what they’re using works can sometimes have an effect on someone’s health. But while a placebo may work for one person, we can’t know it will work for another.</p>
<p>Next, if the Smiths were using the untested “drugs” alongside normal treatment, it could be just the regular treatment that was working. </p>
<p>And, although rare, some cancers can go into spontaneous remission. In these cases, the cancer would have been cured regardless of what John or Jane was taking.</p>
<p>Finally, it’s important to remember when reading about cancer cures from less stringent sources that there can be <a href="http://skepdic.com/selectionbias.html">selection bias</a>. For every miracle cure story you read on a website (<a href="http://www.royalqueenseeds.com/blog-can-you-use-medical-marijuana-for-cancer-treatment--n56">like this one</a>) or on social media, there are thousands of stories of where it didn’t work that don’t make the cut. People don’t write about the failures.</p>
<p>So before you get excited about claims of a cancer cure, make sure you do your homework and determine whether the results are reliable, significant and not biased.</p><img src="https://counter.theconversation.com/content/36344/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nial Wheate in the past has received funding from the ACT Cancer Council, Tenovus Scotland, Medical Research Scotland, Scottish Crucible and the Scottish Universities Life Sciences Alliance for research into anticancer drugs. He is a current committee member of the Royal Australian Chemical Institute's NSW Pharmaceutical Science Group.</span></em></p>Cancer is big news; we often hear of some kind of cure for some version of the illness. But whether it’s a “natural cure” or a promising molecule on its way to becoming a new medicine, there are ways non-scientists…Nial Wheate, Senior Lecturer in Pharmaceutical Chemistry, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/342692014-11-16T09:25:25Z2014-11-16T09:25:25ZMissing data may hold the key to finding new cancer treatments<figure><img src="https://images.theconversation.com/files/64609/original/9r4zwn5x-1415986030.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The answer's in there somewhere ...</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/bunchesandbits/4106216129/in/photolist-7fRqZP-7NLjJ1-ektUTA-2j4nGc-5FXaDU-4hSsNV-84kmXT-4zPuta-4gfNhz-dMoKLk-6B6TBB-en62JV-hH54JL-98Nt9g-dHr1Ed-5Da371-68ASTh-6DobSF-agQKVV-9VATSc-98NsUX-4YqYBt-24Z39z-2NJxPz-5zRG1q-9VDTvQ-aPfT7t-aPfTfD-9VDNKh-fQ6CnH-adZmEd-2tGzTk-5Qjix-68C3ry-68xPxD-doYzvs-LYqeS-fdSzhc-3erG2C-aEnUMn-dDp1UY-dDp2a3-dDiCPz-rfYQd-aj5Mpb-6hndgR-76mFYr-9rW1ZD-Hko71-Hks5p">Bunches and bits</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p>Imagine trying to follow a complex novel many times longer than War and Peace with hundreds of characters and twists. With every cancer having a unique story hidden inside its genetic code, this is similar to the challenge facing modern researchers. </p>
<p>Now imagine trying to follow the plot when some of the pages are missing. </p>
<p>This week, <a href="http://www.ncbi.nlm.nih.gov/pubmed/25256751">our latest study published in the journal Cancer Research</a>, suggests that such a challenge faces scientists deciphering a cancer’s story. We’ve discovered that the technology we use to “read” cancer’s DNA can sometimes cause pieces of the story to be missed at potentially crucial moments in the plot. It’s as if your eReader or tablet kept inexplicably skipping paragraphs as you tap through a novel.</p>
<p>By identifying this missing data we hope to develop techniques to look more closely to see if these areas contain further clues about how to tackle cancer. </p>
<h2>Written in code</h2>
<p>Every tumour has its own unique story about how it descended from being a normal cell into an invasive cancer. These tales are hidden in the genetic code that serves as the blueprint for each job a cell carries out. And the plot twists that make up the individual cancer story are caused by mistakes, or mutations, in this genetic blueprint. </p>
<p>So finding these mutations is a major challenge, and pinpointing them could help scientists develop new treatments to stop the growth of the cancer cells. </p>
<p>Fortunately, modern gene-reading technology has greatly improved our ability to spot these mutations. In our lab we’ve been using a technique called “Next Generation Sequencing”. Using this technology we can now reveal most of the genetic story of a cancer (more than three billion letters of code) in a single experiment. </p>
<p>But when we were searching genetic data from cancer cells for new mutations to target, we spotted inconsistencies between the different versions of data being shared from research institutes around the world. The question was why.</p>
<p>We wanted to find out if this was a common problem that might be preventing us from finding new cancer-causing mutations. To test this we turned to cancer data from two major online databases – the <a href="http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/">Sanger Institute’s COSMIC database</a>, and the <a href="http://www.broadinstitute.org/software/cprg/?q=node/11">Broad Institute’s Cancer Cell Line Encyclopaedia</a>. </p>
<h2>Same cancer, different stories</h2>
<p>We looked through the databases for where the two institutes had collected genetic data from the same type of cancer cell. If the cancer cells are matched you would expect the results to be similar, but what we found was surprising.</p>
<p>The databases showed that the genetic stories produced by the two institutes only matched for around half of the mutations. And in some instances there was much less agreement. We wanted to know why.</p>
<h2>Missing pages</h2>
<p>We picked out some of the cancer samples and homed in on sections of the story, looking for clues to explain why one institute was detecting a mutation when another institute was not. We found that in many cases, the discrepancies were caused by some samples not being read as completely as others. </p>
<p>When we looked for a reason, we found these poorly read regions often landed in areas where the code was less complex. Paradoxically, simple regions of code were actually making it harder for the gene-reading technology to spot any changes. </p>
<p>Another way to look at it is that in some areas of the cancer story the pages were effectively sticking together. This meant that valuable information was missing and the correct version of events could not be established.</p>
<h2>Are these missing pages important?</h2>
<p>The question is: are these missing data just irrelevant filler or do they contain important information that might reveal the strengths and weaknesses of a cancer? To answer this we used different techniques to look at these hidden areas in lung cancer samples, and found a mutation in a gene called PAK4 that had been previously missed. </p>
<p>When we examined the effects of this mutation we found it had the potential to make cancer cells grow more quickly. This indicates that some of these missing pages might carry important information about how a cancer behaves.</p>
<p>As we move into an era where the genetic history of more and more cancer biopsies are read it is important to understand the limitations of the technology. </p>
<p>This is especially important when genetic information becomes more routinely used to help make decisions about the best treatment for a patient.</p>
<h2>Filling in the gaps</h2>
<p>The good news is that gene reading technology is improving and is beginning to fill in these missing areas. This will help us learn more about these “blind spots” and we can use this information to develop new treatments in the future. </p>
<p>In the meantime, we’ll take a closer look at these regions as we also found other explanations about why the data between institutes does not match up. </p>
<p>So far we’ve pinpointed the location of more than 400 areas of missing data. By homing in on these missing pages we hope to piece together cancer’s complex story and write important new chapters which could one day lead to the development of new treatments for patients.</p><img src="https://counter.theconversation.com/content/34269/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Hudson receives funding from Cancer Research UK.</span></em></p>Imagine trying to follow a complex novel many times longer than War and Peace with hundreds of characters and twists. With every cancer having a unique story hidden inside its genetic code, this is similar…Andrew Hudson, Clinical Fellow, Cancer Research UK Manchester Institute, University of ManchesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/257292014-04-23T11:56:49Z2014-04-23T11:56:49ZNHS watchdog changes could endanger new cancer drugs<figure><img src="https://images.theconversation.com/files/46851/original/5bhddb8w-1398180469.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cancer drugs like trastuzumab may not have been approved under the proposed rules.</span> <span class="attribution"><a class="source" href="http://pl.wikipedia.org/wiki/Plik:HerceptinFab.jpg">RedAndr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The National Institute for Health and Care Excellence (NICE) has published <a href="http://www.nice.org.uk/media/FE2/2B/VBA_TA_Methods_Guide_for_CONSULTATION_upload.pdf">new draft proposals</a> laying out major changes to the way it assesses whether new medicines offer value for money for the NHS. These evaluations are difficult – requiring as they do an assessment of the value of life – but are <a href="http://www.thelancet.com/commissions/delivering-affordable-cancer-care-in-high-income-countries">necessary in all healthcare systems</a> that face spiralling costs worldwide. The new proposals, however, could prevent or delay new and effective drugs from reaching patients with cancer.</p>
<p>The draft proposals show that NICE, the body that decides which drugs are available on the NHS in England and Wales, plans to change the parameters its appraisal committees use</p>
<h2>End-of-life criteria</h2>
<p>Under the current system, NICE gives extra weight in its evaluation of cost-effectiveness if drugs have shown a particular benefit in patients at the end of their lives. The calculations it uses are complex but essentially, if a drug has been shown to add three months of life expectancy to patients who have an incurable illness then the NHS may pay a price significantly higher than it would otherwise pay to roll it out.</p>
<p>The importance of end-of-life criteria is very clear: since 2009, when they were introduced, 12 cancer drugs have been approved on this basis. It is likely that many of these drugs would have been rejected in the absence of end-of-life criteria. The new system proposes to remove the criteria, instead incorporating end-of-life benefit into a broader, less defined measure of what would qualify for a higher price bracket. This risks fewer drug approvals in future.</p>
<p>In addition to removing end-of-life criteria from the drug appraisal system, NICE has also suggested it will remove specific consideration of how innovative a new treatment is. I worry that both of these changes will result in cancer drugs being rejected when under the current system they would have been approved. This could deny cancer patients access to life-extending drugs and dramatically reduce the likelihood of achieving the cancer cures of the future.</p>
<p>At The Institute of Cancer Research in London, we have direct experience of the value of the current drug approval process. For example, a groundbreaking new prostate cancer drug called abiraterone that we discovered has helped thousands of sufferers. Initially approved for patients with late-stage prostate cancer resistant to existing drugs, abiraterone has since gone on to <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1209096">benefit patients in earlier stages of the disease</a>. Yet abiraterone would probably not be approved under the proposed changes.</p>
<h2>Stifling innovation risk</h2>
<p>By omitting specific consideration of innovation, the new guidelines will discourage the more creative, high-risk drug discovery research. Previously, NICE’s cost-benefit analysis allowed innovation to be rewarded by paying more for innovative drugs, although the definition of innovation was quite loose. In the new proposals, the chance to formalise the importance of developing novel treatment types has been overlooked. The consequences could be very damaging.</p>
<p>Innovative cancer drugs are those with new mechanisms of action – particularly precision medicines that act on new molecular targets derived from basic cancer biology research and the latest genomics studies, and also those that exploit cutting edge immunological research. Innovative drugs are tremendously important because they offer the possibility of major breakthroughs that cannot be achieved with those that simply mimic or marginally <a href="http://www.ncbi.nlm.nih.gov/pubmed/22235862">enhance the effects of existing drugs</a>.</p>
<p>In recent years, our understanding of cancer has increased dramatically and we’ve learnt that cancer medicine <a href="http://www.ncbi.nlm.nih.gov/pubmed/23361103">works best when it is personalised</a> to individuals. One of the best examples of developing this kind of personalised, precision medicine is trastuzumab. This has helped extend the lives of breast cancer patients with high tumour levels of the HER2 marker, a protein which drives the growth of their cancer. HER2 is also important in a proportion of stomach cancers and NICE approved trastuzumab use in these patients on the NHS under the old end-of-life criteria. Again, this might not have happened under the new draft proposals. </p>
<h2>Tackling drug resistance</h2>
<p>Innovation is also essential if we are to overcome the massive problem of drug resistance – the most important challenge facing cancer drug discovery and development today. We now know that resistance arises because cancers are extraordinarily variable and versatile in evolving mechanisms to get around the effects of both molecular targeted and conventional drugs.</p>
<p>An example of an innovative approach to tackle resistance is the discovery and development of <a href="http://www.ncbi.nlm.nih.gov/pubmed/22215907">Hsp90 inhibitors</a> – a totally new type of drug that we, and only a few other research centres worldwide, have pioneered. These inhibitors have the exciting ability to target several different cancer molecular weaknesses at once, and so can overcome or even prevent drug resistance.</p>
<p>It took costly, high-risk research to develop Hsp90 inhibitors and they have progressed from being a poorly appreciated drug target to one of the most actively pursued in the drug industry today. Leading Hsp90 inhibitors have shown very encouraging results in trials of patients with HER2-positive breast cancers that have become resistant to trastuzumab and patients with non-small cell lung cancer who have become resistant to the widely used molecular targeted drugs erlotinib and crizotinib.</p>
<p>It would be very disappointing if this sort of innovation is not rewarded when it comes to deciding if the NHS will pay so that patients can benefit.</p>
<p>Another crucial benefit arising from both the end-of-life criteria and the current guidance that promotes innovation is that drugs originally approved for “end-of-life” use very often turn out, later on, to benefit patients with earlier stage cancer – as noted above with abiraterone. Also, the current system provides an initial route into the NHS for innovative drugs, which can then subsequently be shown to be effective in the harder-to-treat cancers, especially by combining them with other drugs. New drug combinations could hold the key to tackling drug resistance for many cancers and encouraging innovation is critical for this.</p>
<h2>Crucial time</h2>
<p>The proposed NICE changes could mean a backward step at a crucial point in the history of cancer drug discovery and development, research and development costs of which are of course very high. Clinical trials are the most expensive part and failure in these is still depressingly common. But the high costs and failure rates are mostly a result of the old one-size-fits-all approach where potential drugs are not targeted to the specific molecular characteristics of individual patients. </p>
<p>The costs of developing personalised drugs will eventually fall because clinical trials supporting drug approval will be smarter, smaller and shorter. Instead of relying on a small number of one-size-fits-all blockbusters, companies will have a larger portfolio of lower volume, personalised precision drugs that are targeted to smaller patient populations. The transition to personalised drugs with reduced prices will take time, but this must happen.</p>
<p>Nonetheless, it’s a hugely exciting time, both in basic cancer research and in creative drug discovery and development. We must not let overly restrictive regulation deprive patients of access to innovative and life-prolonging drugs that are being developed now and in the future.</p><img src="https://counter.theconversation.com/content/25729/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paul Workman works at The Institute of Cancer Research (ICR), London which is involved in cancer drug discovery and development research and operates a Rewards to Discoverers scheme. ICR receives income from sales of abiraterone (Janssen) that are reinvested in research. ICR has licensed intellectual property on HSP90 inhibitors to Vernalis and Novartis and may benefit from future income for research. Paul Workman has previously been a consultant for Novartis and Chroma Therapeutics and is a consultant for Astex Pharmaceuticals and Nextech Ventures. He holds shares in Chroma Therapeutics. He has received grant funding from Cancer Research UK, The Wellcome Trust, Medical Research Council, Vernalis, Janssen, Astex Pharmaceuticals, Chroma Therapeutics and the Kidani Trust.</span></em></p>The National Institute for Health and Care Excellence (NICE) has published new draft proposals laying out major changes to the way it assesses whether new medicines offer value for money for the NHS. These…Paul Workman, Head of the Division of Cancer Therapeutics, Institute of Cancer Research, LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/136132013-10-03T04:32:49Z2013-10-03T04:32:49ZNew pain-free treatment for prostate cancer? Not quite<figure><img src="https://images.theconversation.com/files/31391/original/rmw9hqbv-1379319439.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Focal therapy targets and kills only the index cancer calls using heat, cold, or electric currents.</span> <span class="attribution"><span class="source">Image from shutterstock.com</span></span></figcaption></figure><p>If you or someone close to you has lived with prostate cancer, you’ve probably come across dozens of emerging treatments in your hours of Googling. One such treatment, focal therapy, has been <a href="http://www.abc.net.au/news/2013-04-14/new-pain-free-treatment-for-prostate-cancer/4624104">dubbed</a> the “new pain-free treatment for prostate cancer”. But don’t hold your breath; it’s still in its <a href="http://www.ncbi.nlm.nih.gov/pubmed/20378241">experimental phases</a>. </p>
<p>So, what exactly is focal therapy? And what barriers do we need to overcome before it’s made available?</p>
<p>Prostate cancer is the nation’s second most common cancer, with around <a href="http://www.cancer.org.au/policy-and-advocacy/position-statements/prostate-cancer.html">19,000 new diagnoses</a> each year. This type of cancer is multi-focal, meaning it’s found in more than one location in the prostate at a time. The largest tumour – known as the <a href="http://www.ncbi.nlm.nih.gov/pubmed/20233824">index lesion</a> – is the main cancer that can spread to other parts of the body and lead to a <a href="http://www.ncbi.nlm.nih.gov/pubmed/22077593">reduced rate of survival</a>. </p>
<p>Focal therapy targets and kills only the index cancer cells with either cryotherapy (freezing), high-intensity focused ultrasound (intense heating), laser-induced interstitial thermotherapy (intense heating) and irreversible electroporation (cell destruction). The <a href="http://www.ncbi.nlm.nih.gov/pubmed/22445223">idea is that</a> by not treating the entire prostate, the untoward side effects from surgery or radiotherapy can be avoided.</p>
<p>But focal therapy works on the assumption that this index lesion is primarily responsible for cancer recurring, and that this lesion can reliably be imaged, biopsied and specifically treated. </p>
<p>It also assumes that targeting this lesion for focal treatment may lead to equivalent long-term cancer survivals compared with whole-gland therapies such as surgery or radiotherapy – with fewer side effects. And that if unsuccessful, these therapies can be <a href="http://www.europeanurology.com/article/S0302-2838(12)01557-6/fulltext">introduced safely</a>, without compounding side effects. </p>
<p>But to date, these assumptions are unproven.</p>
<h2>Next steps for research</h2>
<p>It’s too early to routinely recommend focal therapy to treat prostate cancer because key questions remain about its safety and efficacy. More specifically, researchers are investigating the following key areas. </p>
<p>First is whether the index lesion can be accurately identified. While a type of <a href="http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/MRI_scan">magnetic resonance imaging technique</a> called <a href="http://www.jenkinsclinic.org/procedures/multiparametric-mri/">multi-parametric MRI</a> may be able to improve cancer identification within the prostate, it also has the potential to <a href="http://www.ncbi.nlm.nih.gov/pubmed/23159454">miss significant cancers</a>. </p>
<p>Current technology does not allow for a lesion seen on MRI to be reliably seen on an ultrasound, which is technology currently used to perform the biopsy. This means there is the potential for error in both the diagnosis of a cancer (its size, position and how aggressive it is) and its subsequent focal treatment. After all, if you can’t see it, how are you going to biopsy it, yet alone treat it accurately?</p>
<p>Second, cancer control rates following focal therapies are largely unknown compared with standard whole-gland therapies (such as surgery). Added to this, few focal therapy reports have <a href="http://www.ncbi.nlm.nih.gov/pubmed/23265382">systematically reported</a> quality of life outcomes such as incontinence or erectile dysfunction using validated tools. As such, the side effects of these treatments are largely unknown. </p>
<p>Third, the feasibility, efficacy and safety of whole-gland therapies used to salvage failed focal therapy is unknown. And the impact of leaving the non-index lesions untreated is also unknown.</p>
<p>Finally, with no <a href="http://www.ncbi.nlm.nih.gov/pubmed/23265382">no formal definition</a> as to what constitutes treatment failure, there are significant challenges in determining how to monitor patients following focal therapy.</p>
<h2>What does this mean for me?</h2>
<p>Focal therapy isn’t a substitute for active surveillance and men with small, low-risk cancers should be reassured that their risk of cancer death over a 10- to 15-year time frame is extremely low. For these men, it’s safe to monitor the situation and have treatment only if the tumour worsens. This avoids the side effects of unnecessary treatments.</p>
<p>The lack of clear evidence of the superiority of focal therapy (or even equivalence) to standard therapies in cancer outcomes, and the largely unknown spectrum and severity of side effects, should not be understated. So if you do need treatment, opt for one of the proven effective therapies such as surgery or radiotherapy.</p>
<p>If you do wish to undergo focal therapy, it’s important you do so as part of a formal clinical trial, with appropriate ethics committee approval, consent process and with strict reporting requirements regarding outcomes and safety profile. </p>
<p>Is focal therapy worth studying scientifically? The answer is absolutely yes, but under formal clinical trial conditions. Is it ready for prime time? Not in 2013.</p><img src="https://counter.theconversation.com/content/13613/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Frydenberg is Vice President , Urological Society of Australia and New Zealand </span></em></p>If you or someone close to you has lived with prostate cancer, you’ve probably come across dozens of emerging treatments in your hours of Googling. One such treatment, focal therapy, has been dubbed the…Mark Frydenberg, Head of Urology at Monash Medical Centre and Associate Professor of Surgery, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/178992013-10-02T05:49:59Z2013-10-02T05:49:59ZSwarms of robots could fight cancer (with your help)<figure><img src="https://images.theconversation.com/files/31469/original/nrwfrgw2-1379416904.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Exterminate!</span> <span class="attribution"><span class="source">Roj</span></span></figcaption></figure><p>Cancer researchers are not shy of using <a href="http://crnano.org/whatis.htm">nanotechnology</a>. Their work is making promising headway into developing safer and more effective treatments. And now, new developments in the area mean that the general public <a href="http://nanodoc.org/">can help</a> through <a href="https://theconversation.com/explainer-what-is-citizen-science-16487">crowdsourcing</a>. </p>
<p>Cancer causes one in every four deaths in the US, and an estimated <a href="http://www.cancerresearchuk.org/cancer-info/cancerstats/world/cancer-worldwide-the-global-picture">12.7 million new cancer cases</a> were diagnosed worldwide in 2008. Current treatments are far from ideal. For example, typical chemotherapies seep out of the blood stream after injection and spread throughout the body. The drugs are then free to attack all the cells encountered – even healthy ones - causing significant side effects. </p>
<p>This is obviously far from ideal. Bioengineers are therefore experimenting with <a href="http://www.sciencedaily.com/articles/n/nanoparticle.htm">nanoparticles</a> that can deliver drugs and diagnostics directly to tumours. Nanoparticles are slightly bigger than drugs: around five to 500 nanometers, which is around 100 to 10,000 times smaller than a human hair. This special size allows them to leak out of the large pores in tumour vessels, and yet still be contained in the blood stream throughout the rest of the body. As a result, nanoparticles can <a href="http://www.ncbi.nlm.nih.gov/pubmed/20441782">passively accumulate in tumours</a> while avoiding healthy tissue.</p>
<p>Nanoparticles come in different sizes, shapes and materials. They can be loaded with drugs that are released in a controlled fashion and coated with molecules that allow them to interact with their environment. Some of these molecules can be a signature to uniquely identify cancer cells. Upon binding, cells can engulf nanoparticles that then deliver their cargo within the cell. </p>
<p>There are many ways you can design a nanoparticle. Depending on your design, the nanoparticle will move, sense and act in different ways – just like a robot. Control is in the design of the nanoparticles and their interactions with the environment, rather than any intelligence inside it. In other words, changing the body of the nanoparticle will change its behaviour: we call it embodied intelligence. </p>
<p>The challenge is understanding which nanoparticle design will improve treatment outcome. This is a difficult problem because trillions of nanoparticles interact in a tumour with millions of cells. Predicting and optimising the behaviour of all these nanoparticles in such a complex system is guess work at best.</p>
<h2>Swarm Control</h2>
<p>Like our nanoparticles, flocks of birds, ant colonies, cells and robot collectives can exhibit seemingly complex swarm behaviours when large numbers of simple agents react to local information. Our goal now is to explore how nanoparticles can cooperate, or swarm, to synergistically improve their therapeutic effect.</p>
<p>Recent work by <a href="http://lmrt.mit.edu/">the Bhatia Laboratory at MIT</a> shows promise <a href="http://www.nature.com/nmat/journal/v10/n7/full/nmat3049.html">in this direction</a>. Gold nanoparticles would passively accumulate in the tumour. The nanoparticles would then be heated using a laser, thereby causing damage to the tumour tissue. The second wave of nanoparticles, engineered to bind to the damaged tissue, would therefore accumulate at higher numbers there.</p>
<p>Using a simulator that models how nanoparticles interact with each other and the tumour environment, we can now explore such nanoparticle swarm designs. In the video example below, simulated nanoparticles leaving a blood vessel (in red) must find a rare cell (with a pink border) in the tumour tissue. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/MH4UAPdoZxg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>This rare cell could have a specific mutation, and its detection might help identify a pocket of cells resistant to treatment. By smartly engineering the nanoparticles and how they interact with their environment, we are able to mark direct paths from the vessels to the cell. Similar to ants forming trails to reach your picnic table, these nanoparticles work by depositing and interacting with information in the environment.</p>
<p>There are many such tumour scenarios and swarm strategies. Each one takes time to explore and requires large amounts of trial and error. Also, each problem is different, making it difficult to program a computer that can automatically design the nanoparticles. </p>
<p>Crowdsourcing therefore allows bioengineers and the general public to imagine new nanoparticle strategies towards the treatment of cancer. The simulator called <a href="http://nanodoc.org/">Nanodoc</a> predicts how nanoparticles behave in tumours and is based on years of research. The hope is that people using the simulator can help discover new, creative and efficient nanoparticle strategies that we haven’t thought of in the lab. </p>
<hr>
<p><em>This an edited version of a post first published on <a href="http://robohub.org/crowdsourcing-nanomedicine-for-cancer-first-steps-towards-swarming-nanobots/">RoboHub</a>.</em></p><img src="https://counter.theconversation.com/content/17899/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sabine is involved in the development of Nanodoc game. By reading this article you may help science by being tempted to try out the game.</span></em></p>Cancer researchers are not shy of using nanotechnology. Their work is making promising headway into developing safer and more effective treatments. And now, new developments in the area mean that the general…Sabine Hauert, Human Frontier Science Program Cross-Disciplinary fellow, Massachusetts Institute of Technology (MIT)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/166412013-08-15T05:38:46Z2013-08-15T05:38:46ZBurden of brain disorders ignored by government<figure><img src="https://images.theconversation.com/files/29189/original/z2yhrk78-1376412307.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C851%2C564&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Head for numbers: research into brain disorders is seriously underfunded.</span> <span class="attribution"><span class="source">Pennstatenews</span></span></figcaption></figure><p>According to various large-scale studies conducted by the <a href="http://www.who.int/en/">World Health Organization</a>, about a <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039289/">third of the adult worldwide population</a> suffer from a mental disorder such as depression, anxiety and schizophrenia. </p>
<p>Taken together with neurological disorders, such as dementia and stroke, these “disorders of the brain” account for <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173804/">13% of the global disease burden</a>. This surpasses both <a href="http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf">cardiovascular diseases (5%) and cancer (10%)</a>. </p>
<p>Such statistics may be surprising as there is a general lack of awareness regarding the pervasiveness of brain disorders. However, global data or even just <a href="http://www.ecnp.eu/%7E/media/Files/ecnp/communication/reports/ECNP%20EBC%20Report.pdf">within the European Union</a>, can only serve as a wake-up call.</p>
<h2>Matching data to policy</h2>
<p>And since the amount of money available to invest in health research is restricted in times of economic austerity, government policy to tackle the problem in the UK must be based on specific cost data. </p>
<p>A <a href="http://jop.sagepub.com/content/early/2013/07/25/0269881113495118.full.pdf">recent study</a> we carried out in collaboration with researchers from University of Cambridge, Hertfordshire University, Imperial College London, University College London, University of Leeds and University of Manchester revealed that the total estimated cost of major brain disorders in the UK was about £112 billion in 2010. </p>
<p>This estimate was derived from “bottom-up” calculations where possible: the total number of diagnosed cases in the UK - about 45m - was multiplied by the health cost per person calculated from interviews, questionnaires and medical records collected on each major brain disorder. </p>
<p>Due to limitations in data, the costs for certain disorders were not included. Therefore, the estimate of the total cost can be considered conservative. Our study also provides estimates for the total costs incurred by individual brain disorders.</p>
<h2>The five most expensive disorders</h2>
<p>In 2010, the five most expensive disorders in the UK were: dementia (£18.6 billion), mood disorders (£16.1 billion), psychotic disorders (£14 billion), addiction (£9.8 billion) and anxiety disorders (£9.8 billion). Using this data when planning and implementing national health policies will ensure that money is spent in the right place and as efficiently as possible.</p>
<p>Particular attention should be paid to dementia, which was the most expensive brain disorder. In view of an ageing population, we can only expect these costs to increase in future. </p>
<p><a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2011.03500.x/abstract">Another study</a> which directly compared the costs of dementia in the UK with stroke, cancer and coronary heart disease (CHD) estimated that the cost of dementia on the social care system was significantly higher. Combining health and social care, informal care and productivity losses, dementia had the highest annual cost at £23 billion, followed by cancer (£12 billion), CHD (£8 billion) and stroke (£5 billion).</p>
<p>More importantly, our study found that about half of overall health costs of brain disorders were indirect, for example lost economic productivity due to work absence or early retirement. The remaining costs were divided equally between direct healthcare costs, for example visits to the doctor, hospitalisation and medicines, and direct non-medical costs such as use of social services, special accommodation and informal care. </p>
<p>This implies that more effective treatment, both pharmacological and psychological, has the potential to considerably reduce the overall economic burden to society but also improve patients’ quality of life. This is a clear argument for investing in research that leads to a better understanding of how to most effectively prevent, diagnose early, treat and manage brain diseases.</p>
<p>Although we have made great progress in understanding the brain within the last few decades, there are still substantial gaps in our knowledge, which hinders development of more effective treatments and preventive interventions for such neuropsychiatric disorders.</p>
<h2>The true economic burden</h2>
<p>However, despite UK government recommendations that health research priorities should be informed by the size of a disease’s impact on the population and economy, the majority of health research funding in the UK has historically been directed towards cancer (£590m). </p>
<p>Research spending on brain disorders, such as dementia (£50m) and stroke (£23m), has been comparatively seriously underfunded. </p>
<p>The reasons for these disparities are not well understood and are likely to be complex. They may include ignorance of the magnitude of brain disorders, an historical sense of tolerance or therapeutic nihilism (“what’s the point?”) as well as marginalisation and stigma associated with certain brain disorders. </p>
<p>In addition, the worldwide withdrawal of pharmaceutical companies from key areas of clinical neuroscience research poses an additional threat for the advancement of treatments for brain disorders. </p>
<p>We need to transform how funding is allocated, with the focus on distributing funding according to the overall economic burden of the diseases. </p>
<p>And we now have substantial knowledge about brain disorders and excellent technology to make <a href="http://www.nature.com/nature/journal/v483/n7389/full/483269a.html">rapid advances</a> to further understand the underlying mechanisms of brain disorders, <a href="http://www.ncbi.nlm.nih.gov/pubmed/23563062">new treatments</a> and prevention. Given appropriate resources, we could improve brain health for all members of society based on sound evidence.</p><img src="https://counter.theconversation.com/content/16641/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Barbara Sahakian consults for Cambridge Cognition, Servier and Lundbeck. She holds a grant from Janssen/J&J. She holds shares in CeNeS. She is President of the British Association for Psychopharmacology.</span></em></p>According to various large-scale studies conducted by the World Health Organization, about a third of the adult worldwide population suffer from a mental disorder such as depression, anxiety and schizophrenia…Barbara Jacquelyn Sahakian, Professor of Clinical Neuropsychology, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/169192013-08-13T05:27:13Z2013-08-13T05:27:13Z‘Mitotic spindles’ could help develop better chemo drugs<figure><img src="https://images.theconversation.com/files/29073/original/9bdwbfy9-1376302663.jpg?ixlib=rb-1.1.0&rect=1%2C0%2C1022%2C683&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A good yarn: chromosomes are shared out to dividing cells by mitotic spindles.</span> <span class="attribution"><span class="source">Triesquid</span></span></figcaption></figure><p>Cells use a tiny machine called the mitotic spindle to share genetic material equally between cells when they divide. But when this process goes wrong it can lead to cancer. </p>
<p>For many years we’ve been interested in how the spindle divides up genetic material accurately. When a cell divides it must make sure that each daughter cell receives just one copy of each chromosome, which carries DNA to the new cell. Defects in this process can lead to cells having the wrong amount of chromosomes, which can lead to cancer or birth defects.</p>
<p>Anti-cancer drugs have been developed which target the mitotic spindle and destroy dividing cells in tumours. But these drugs have significant side effects. In my lab, we’re trying to understand how the mitotic spindles work in order to develop drugs that are more targeted and have fewer side effects.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/29083/original/2hntmvff-1376311514.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/29083/original/2hntmvff-1376311514.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=447&fit=crop&dpr=1 600w, https://images.theconversation.com/files/29083/original/2hntmvff-1376311514.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=447&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/29083/original/2hntmvff-1376311514.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=447&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/29083/original/2hntmvff-1376311514.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=562&fit=crop&dpr=1 754w, https://images.theconversation.com/files/29083/original/2hntmvff-1376311514.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=562&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/29083/original/2hntmvff-1376311514.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=562&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mitotic spindle: chromosomes in blue, microtubles in green.</span>
<span class="attribution"><span class="source">Wikimedia Commons/Afunguy</span></span>
</figcaption>
</figure>
<p>Chromosomes are allocated by the mitotic spindle, which is made up of many thin filaments called microtubules. These are held together in bundles and these bundles share the chromosomes equally during mitosis.</p>
<p>Colleagues and I at Warwick Medical School have shown <a href="http://bit.ly/1boixL1">in a paper published</a> in The Journal of Cell Biology that a team of three proteins - called the TACC3–ch-TOG–clathrin complex - work to hold the spindle’s microtubules together and stabilise the bundle through a system of “bridges”. Drugs such as Taxol (Paclitaxel) have been used very effectively in chemotherapy because they poison microtubles and inhibit the mitotic spindle. This stops cancer cells from dividing and causes them to die. </p>
<p>However, the disadvantage is that microtubules are needed for many functions in non-cancerous cells. This means that existing treatments don’t discriminate between cancerous and normal cells. So the use of Taxol and others in its family, for example, cause side effects such as nerve damage. If we could target the mitotic spindle proteins, rather than microtubules, we may be able to develop effective anti-cancer drugs with far fewer side effects.</p>
<p>We’ve found that in cancer cells, the amount of the protein complex is either too low or too high. This suggests that these proteins could be targeted for potential anti-cancer therapies in the future.</p>
<p>Our research group, together with Richard Bayliss’ lab at the University of Leicester, have recently described how the proteins in the TACC3–ch-TOG–clathrin complex bind to one another. In turn this led us to understand how the complex binds to microtubules. By taking out the TACC3 protein, the clathrin loses its function and is no longer able to create some of the bridges that bind the microtubles. </p>
<p>It’s important as we can use this information to think of ways to break the complex apart or to prevent it binding microtubules. From this, we may be able to disrupt the function of the protein complex in dividing cells and inhibit the sharing of chromosomes during mitosis, causing the death of cancerous cells. </p>
<p>The research is in the early stages, but we have also discovered that an enzyme called Aurora A kinase controls the assembly of the protein complex. Aurora A is often amplified in tumours and clinical trials into inhibiting its role are already underway into drugs that cause the TACC3-ch-TOG-clathrin complex to fall apart and actually break away from the mitotic spindle altogether. </p>
<p>When treating cancer we still often cause damage in other areas. Understanding and controlling the action of the mitotic spindle could help us to better target treatment by directly shutting down defective cells.</p><img src="https://counter.theconversation.com/content/16919/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steve Royle is a Senior Fellow for Cancer Research UK which funds his lab at Warwick University.</span></em></p>Cells use a tiny machine called the mitotic spindle to share genetic material equally between cells when they divide. But when this process goes wrong it can lead to cancer. For many years we’ve been interested…Steve Royle, Associate Professor, University of WarwickLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/160932013-07-17T05:39:24Z2013-07-17T05:39:24ZHippos and bumblebee bats can teach us about cancer<figure><img src="https://images.theconversation.com/files/27482/original/m4kcj3d7-1373893010.jpg?ixlib=rb-1.1.0&rect=3%2C0%2C2498%2C1565&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">How does a hippo know it should be big?</span> <span class="attribution"><span class="source">PA/David Cheskin</span></span></figcaption></figure><p>Mammals display an incredible diversity in size. The largest mammal, the blue whale, can grow up to 30m long and weigh up to 200 tonnes. Now compare that to the Bumblebee bat, which is 3cm long and weighs in at only 2g. </p>
<p>To put these figures into perspective: 30m is as tall as the ten-story <a href="http://www.youtube.com/watch?v=2NXK8pkL8ec">Instacon building</a> that was recently built in India; 200 tonnes is the weight of a 747 airliner; and a banknote can weigh 1g.</p>
<h2>Size matters</h2>
<p>So how does a blue whale “know” to be that big? And why don’t we have <a href="http://www.youtube.com/watch?v=G9hJK4fCq4U">tiny hippos</a> or enormous mice? And what can size control in mammals tell us about cancer and regenerative medicine?</p>
<p>The organs of animals are proportional to body size. The blue whale’s heart weighs 600kg and is the size of a small car while our lungs fit perfectly within our chest. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=393&fit=crop&dpr=1 600w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=393&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=393&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=494&fit=crop&dpr=1 754w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=494&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=494&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">He’s having a whale of a time.</span>
<span class="attribution"><span class="source">PA/David Parry</span></span>
</figcaption>
</figure>
<p>But if you compare cells taken from a whale and a miniature bat, they are the same size. We know then that the size of an animal is controlled by the number of cells in each tissue. And it’s the balance between cell growth and cell death that controls when an organ stops growing. </p>
<p>As cancer is caused by uncontrolled growth of cells, a better understanding of how cells decide to grow or die has important ramifications for health and disease.</p>
<h2>The Hippo pathway</h2>
<p>It has only been in recent years that the molecular and cellular pathways that control organ size have been studied. It has been known for many years that when cells grow in a test tube, they stop dividing when they come in contact with other cells. </p>
<p>This “cell-contact” mechanism mediates growth and is defective in cancer cells, which continue to grow even when they are extremely crowded. </p>
<p>In many animals, including flies, mice and humans, tissue overgrowth is triggered by faulty signalling systems. One of these signalling systems was recently identified and called the <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124840/">Hippo pathway</a>, a tongue-in-cheek nod to the size of hippos. </p>
<p>Mutations in this pathway lead to a massive increase in organ size because of uncontrolled growth of cells. There is now an explosion of research into how the Hippo pathway is regulated in normal tissue, as well as during cancer. But our new study, published last week in <a href="http://bit.ly/18lFXD4">Developmental Cell</a>, identifies a novel mechanism that controls this pathway.</p>
<p>The Hippo pathway is activated by contact with cells. When that happens, chemical signals within the cell cause a protein called Yap - or Yes-associated protein - to be switched off. The Yap protein causes cells to recognise that it’s time to stop dividing but if the signalling system is faulty, Yap isn’t inactivated and tissue and organs continue to grow.</p>
<p>We’ve seen it in flies or mice that lack the ability to inactivate Yap - cells continue to grow, leading to larger organs and ultimately cancer.</p>
<h2>Using proteins to send messages</h2>
<p>Signalling pathways use several proteins in the body to pass along a message from outside the cell into the nucleus of the cell, which changes the way the cell behaves. How proteins pass along this signal varies depending on what the ultimate message is. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=821&fit=crop&dpr=1 600w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=821&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=821&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1032&fit=crop&dpr=1 754w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1032&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1032&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A Yes-Association protein gets the chemical treatment.</span>
<span class="attribution"><span class="source">Flickr/Nikki Pugh</span></span>
</figcaption>
</figure>
<p>A common way the body creates different messages is by using chemicals to modify proteins, which then affects their ability to interact with the next link in the chain. </p>
<p>For the Hippo pathway and inhibiting cell growth, it’s the addition of a phosphate group of chemicals on the Yap protein that inactivates it. Our results also identify that an additional chemical modification - methylation - controls how Yap works - and ultimately the way the Hippo pathway works.</p>
<p>When we began this project, our focus wasn’t turned towards this signalling system but on the role of an enzyme called Set7. But differences we saw in the structure of the gut in the mice we studied and the publication of the another study into the characteristics of mice that had a mutation in their Hippo pathway, led to a series of experiments also linking Set7 and a role in inhibiting Yap - and therefore cell growth.</p>
<h2>Cancer drugs</h2>
<p>The ramifications of our findings are diverse. Our findings suggest that drugs that can block Set7’s function could result in more cell growth, which could improve regenerative processes such as tissue repair in people who have suffered damage. </p>
<p>But activation of Set7 could potentially increase the inhibition of Yap and thereby slow cell growth, creating a potential new cancer therapy. </p>
<p>We have yet to work out whether manipulation of Set7 during foetal development would have any drastic effect on tissue size - allowing us to create giant bumblebee bats for example. Or whether Set7 works differently in small or large animals. And for now, we still have very little understanding of all of the intricacies of this exciting Hippo pathway. </p>
<p>So unfortunately it will still be a while until <a href="http://www.youtube.com/watch?v=G9hJK4fCq4U">house hippos</a> are a reality.</p><img src="https://counter.theconversation.com/content/16093/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Colby Zaph receives funding from the Canadian Institutes of Health Research.</span></em></p>Mammals display an incredible diversity in size. The largest mammal, the blue whale, can grow up to 30m long and weigh up to 200 tonnes. Now compare that to the Bumblebee bat, which is 3cm long and weighs…Colby Zaph, Assistant professor of Pathology and Laboratory Medicine , University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.