tag:theconversation.com,2011:/uk/topics/pancreatic-cancer-4151/articlesPancreatic cancer – The Conversation2023-06-16T15:56:00Ztag:theconversation.com,2011:article/2076582023-06-16T15:56:00Z2023-06-16T15:56:00ZKeto diet may slow cancer tumour growth in mice – but not without potentially deadly consequences<figure><img src="https://images.theconversation.com/files/532367/original/file-20230616-17-p00ign.jpg?ixlib=rb-1.1.0&rect=8%2C8%2C5982%2C3979&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The keto diet is very low in carbohydrates.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/keto-ketogenic-diet-low-carb-healthy-1075530926">SewCreamStudio/ Shutterstock</a></span></figcaption></figure><p>The ketogenic (keto) diet has been popular in recent years among people looking to lose weight and keep fit. But what many people don’t realise is that this low carb, high-fat diet has actually been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/">used for centuries</a> in the treatment of medical maladies, such as epilepsy. More recently, researchers have been investigating its use alongside chemotherapy to improve remission and survival in patients with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/">advanced metastatic cancers</a>.</p>
<p>A <a href="https://www.sciencedirect.com/science/article/abs/pii/S1550413123001857?via%3Dihub">recently published study</a> in mice has now shown that the keto diet may also have use in treating tumours. But while the diet appeared to slow the tumour growth in mice with colorectal and pancreatic cancers, it was also shown to accelerate the onset of cachexia – a severe wasting disease thought to cause <a href="https://www.cancer.gov/about-cancer/treatment/research/cachexia#:%7E:text=Cachexia%20is%20estimated%20to%20occur,failure%20related%20to%20muscle%20loss.">30% of all cancer-related deaths</a>. </p>
<p>To conduct their study, the authors selected two types of mice that were predisposed to cachexia. They then transplanted half of them with colorectal cancer and induced pancreatic cancer in the other half. The mice were then allocated into two groups: one group was fed a standard diet while the other group was fed a high-fat, low carb keto diet.</p>
<p>Over the course of the next month, the investigators found that mice on the keto diet showed slower tumour growth than the mice fed a standard diet. However, it also appeared that the keto diet was associated with shorter survival times due to the faster onset of cachexia. </p>
<h2>Keto and cancer</h2>
<p>The reason the ketogenic diet works to slow the growth of tumours is down to the way in which cancer cells metabolise their “food” compared to normal, healthy cells. </p>
<p>All the cells in our bodies get their energy from glucose (sugar) first and foremost, and then from fats. Since cancer cells grow quickly, they have much higher energy needs – so they rely solely on glucose for energy. </p>
<p>Glucose is released from the carbohydrates we’ve eaten as they’re broken down in our bodies. But since the keto diet has a very low carbohydrate intake, it’s thought that this “starves” the cancer cells of the energy they need to grow. This is what the authors were able to demonstrate in their study.</p>
<p>Keto also kick-starts a process called <a href="https://www.sciencedirect.com/science/article/abs/pii/S1550413123001857?via%3Dihub">lipid peroxidation</a>, which causes the body to use fats for the energy it needs instead. However, this process also creates a number of highly reactive molecules as a by-product which need to be cleared from the body before they cause further cell damage. </p>
<figure class="align-center ">
<img alt="A digital illustration of a cancer cell." src="https://images.theconversation.com/files/532368/original/file-20230616-17-npaaeo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532368/original/file-20230616-17-npaaeo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532368/original/file-20230616-17-npaaeo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532368/original/file-20230616-17-npaaeo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532368/original/file-20230616-17-npaaeo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532368/original/file-20230616-17-npaaeo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532368/original/file-20230616-17-npaaeo.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">Cancer cells have higher energy needs.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/cancer-cell-human-body-340710245">Crevis/ Shutterstock</a></span>
</figcaption>
</figure>
<p>Since the mice’s cells lacked an adequate energy supply to quickly remove these highly reactive molecules, this led to an increase of a molecule called GDF-15 which suppressed their appetite and contributed to their weight loss.</p>
<p>The researchers also found that the keto diet impaired the production of corticosteroids – naturally-occurring hormones which help reduce inflammation and regulate the immune system. This accelerated the onset of cachexia in the mice, shortening their overall survival.</p>
<p>Interestingly, when the researchers treated the mice with an injection of dexamethasone – a corticosteroid drug that counteracts the stress hormone cortisol and is often used to treat various cancer-related conditions, such as anemia – they were able to delay the onset of cachexia and improve their overall survival. </p>
<h2>Cancer treatment</h2>
<p>Although it’s tempting to draw conclusions from this research, it’s also important to bear a few things in mind. </p>
<p>First, this study was performed in mice – and of course, we aren’t mice. It’s imperative that further research be carried out to see whether the keto diet has a similar effect in humans – and crucially, whether treatment with dexamethasone delays the onset of cachexia in humans, too. At the moment, there are a <a href="https://clinicaltrials.gov/ct2/results?cond=cancer&term=ketogenic+diet&cntry=&state=&city=&dist=&Search=Search">number of ongoing trials</a> and some <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/">emerging evidence</a> suggesting the keto diet has beneficial effects on many types of cancer.</p>
<p>Second, patients who follow a keto diet will experience different benefits depending on the stage of their cancer. For example, studies in cells have shown fasting or following the keto diet while undergoing chemotherapy may improve <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608686/">how responsive the cancer is</a> to chemotherapy – while also reducing damage to nearby healthy tissues.</p>
<p>This is because fasting (and keto) act like a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938162/#:%7E:text=Fasting%20or%20fasting%2Dmimicking%20diets,the%20effects%20of%20cancer%20therapies.">“magic shield”</a>, protecting healthy cells from <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190229/">chemotherapy-induced damage</a>. </p>
<p>Fasting shuts down all non-essential processes, including metabolism. However, cancer cells ignore this message and continue growing. Chemotherapy targets rapidly growing cells – and so in a fasted state, it will target the cancer cells instead, leaving healthy cells safe.</p>
<p>Although this latest study demonstrates that the keto diet may also have the harmful effect of accelerating cachexia in mice, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471358/#B65-nutrients-13-03202">several studies</a> looking at the effect of a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314860/">keto diet on pancreatic cancer</a> actually find keto <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471358">protects against muscle loss</a>. </p>
<p>These differing results may be down to the methods used in each of these studies, with some experiments being conducted in cells, and others in mice. But given these contradictory findings, it will be important for more detailed investigations to be done.</p>
<p>While evidence suggests keto may have benefits for slowing cancer growth, less is known about any adverse effects it may have (such as accelerating cachexia). Given there’s still so much we don’t know, it’s advised that patients undergoing cancer treatment speak with their medical practitioner about any diet changes they may be planning to make.</p><img src="https://counter.theconversation.com/content/207658/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mhairi Morris 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 diet was shown to accelerate onset of a severe wasting disease.Mhairi Morris, Senior Lecturer in Biochemistry, Loughborough UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2056062023-05-19T14:52:44Z2023-05-19T14:52:44ZPancreatic cancer: a personalised mRNA vaccine may boost effects of treatment<figure><img src="https://images.theconversation.com/files/527196/original/file-20230519-27-z54c2x.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5991%2C3988&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Immunotherapies, such as cancer vaccines, help train the immune system to fight off cancer.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-doctors-hand-purple-gloves-holding-1788967661">Pand P Studio/ Shutterstock</a></span></figcaption></figure><p>Pancreatic cancer is one of the <a href="https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer#heading-One">deadliest types of cancer</a>. This is largely due to the fact that pancreatic cancer symptoms typically don’t arise until the late stages of the disease, making many patients ineligible for the current best treatment method, which is surgery to remove any tumours. </p>
<p>Even in patients who have tumours removed, there’s often a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679234">really high chance</a> of the cancer returning.</p>
<p>But the results of a recent study suggest that the immune system could be a useful tool in treating pancreatic cancer. The research, which was published in <a href="https://www.nature.com/articles/s41586-023-06063-y">Nature</a>, showed a personalised cancer vaccine was able to stimulate the immune system in half of the patients who received it. </p>
<p>This heightened immune response was also still detectable in these patients a year and a half later.</p>
<p>In order to understand how this pancreatic cancer vaccine works, it’s important to first understand the role that the immune system plays in preventing cancer.</p>
<p>Our immune system is often very well equipped to fight cancer. But unfortunately, cancer cells contain certain protein receptors whose purpose is to help them hide from our immune cells – effectively preventing our immune system from destroying them. </p>
<p>However, scientists have found a way to block these receptors, so the immune system is able to recognise cancer cells as a threat again and remove them.</p>
<p>This is what <a href="https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/what-is-immunotherapy.html">immunotherapy</a> – one of the newest techniques for treating cancer – does. These therapies work by harnessing the power of the immune system.</p>
<p>There are a few different types of immunotherapies, but a new one that is promising against cancer is the use of mRNA vaccines. These use genetic material in order to stimulate the immune system.</p>
<p>Scientists first begin by taking the genetic material of cancer cells and identifying the most mutated parts of the DNA – so-called neoantigens – before putting them in between a strand of mRNA. </p>
<p>If we think of DNA as the hard drive, mRNA is sort of like the software of our cells. It’s function is essentially to copy and carry genetic instructions from our DNA to other parts of the cell.</p>
<p>This mRNA is then given to patients as a personalised vaccine. It’s personalised because everyone has different neoantigens, so everyone receives slightly different vaccines with slightly different mutations encoded into the mRNA strand. </p>
<p>Once injected into the patient, the mRNA then makes a little bit of the cancer – just enough to stimulate the immune system. The idea is that the person’s immune systems will then react to the cancer and give them protection.</p>
<p>This is how the recent pancreatic cancer mRNA vaccine was developed. The pharmaceutical company BioNtech created personalised mRNA vaccines for 16 participants using cells from their recently removed tumours.</p>
<figure class="align-center ">
<img alt="A digital drawing of T cells attacking a cancer cell." src="https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.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">Half of the participants had an increase in T cell levels.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/tcells-work-fight-cancer-immunotherapy-car-1972711475">Design_Cells/ Shutterstock</a></span>
</figcaption>
</figure>
<p>The patients were all treated with this personalised vaccine, alongside another form of immunotherapy (the drug atezolizumab) followed by aggressive chemotherapy. </p>
<p>Half of the patients treated with the vaccine and immunotherapy combination saw an increase in a specific type of immune cell (called a T cell, which is known to protect against cancer). This showed the researchers that for at least some participants, their immune systems might be learning to fight the cancer.</p>
<p>At an 18-month follow-up, the patients who’d seen the increase in T cells still had signs of improved immune response. Most also had no signs of their cancer recurring. </p>
<p>The authors concluded that it may be because the immune system was successfully stimulated which helped stop the cancer returning. The mRNA vaccine was also well tolerated by patients with no obvious major side effects.</p>
<h2>Immune function</h2>
<p>While this trial’s findings are intriguing, its numbers are too small to draw any major conclusions. It will be necessary for larger trials to be conducted including randomised studies. </p>
<p>This would see only some of the participants receive the vaccine, allowing researchers to truly understand what effect it has – and whether the vaccine really does what it’s supposed to do, which is stimulate the immune system and improve time before recurrence (and ultimately survival). </p>
<p>This would also allow them to see whether the vaccine had a distinct effect, and that this effect wasn’t just down to the other treatments or immunotherapy the participants received.</p>
<p>It’s promising to see that we may have a new type of therapy to investigate for treating pancreatic cancer. These findings also highlight the potential of mRNA vaccines as a cancer treatment more broadly – building on the results of another study from last year which showed an mRNA vaccine to be <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-merck-vaccine-combo-cut-melanoma-recurrence-by-44-study-2022-12-13/">effective against melanoma</a>.</p><img src="https://counter.theconversation.com/content/205606/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Justin Stebbing is editor-in-chief of Oncogene. His conflicts are listed here and none are relevant to this piece:
<a href="https://www.nature.com/onc/editors">https://www.nature.com/onc/editors</a></span></em></p>This study further highlights the potential of mRNA vaccines in cancer treatment.Justin Stebbing, Professor of Biomedical Sciences, Anglia Ruskin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1977682023-01-16T16:05:12Z2023-01-16T16:05:12ZStopping the cancer cells that thrive on chemotherapy – research into how pancreatic tumors adapt to stress could lead to a new treatment approach<figure><img src="https://images.theconversation.com/files/504479/original/file-20230113-18-eznoq2.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2414%2C2117&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Hypoxia, or a state of low oxygen, can encourage tumors to spread. This microscopy image visualizes the microenvironment of a breast tumor.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/HJpd72">Steve Seung-Young Lee, Univ. of Chicago Comprehensive Cancer Center, National Cancer Institute, National Institutes of Health via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>As with weeds in a garden, it is a <a href="https://www.cancerresearchuk.org/about-cancer/what-is-cancer/why-some-cancers-come-back">challenge to fully get rid of cancer cells</a> in the body once they arise. They have a relentless need to continuously expand, even when they are significantly cut back by therapy or surgery. Even a few cancer cells can give rise to new colonies that will eventually outgrow their borders and deplete their local resources. They also tend to wander into places where they are not welcome, creating metastatic colonies at distant sites that can be even more difficult to detect and eliminate.</p>
<p>One explanation for why cancer cells can withstand such inhospitable environments and growing conditions is an old adage: What doesn’t kill them makes them stronger.</p>
<p>At the very earliest stage of tumor formation, even before cancer can be diagnosed, individual cancer cells typically find themselves in an environment lacking nutrients, oxygen or adhesive proteins that help them attach to an area of the body to grow. While most cancer cells will quickly die when faced with such inhospitable conditions, a small percentage can adapt and gain the ability to initiate a tumor colony that will eventually become malignant disease. </p>
<p><a href="https://scholar.google.com/citations?user=e_INeP8AAAAJ&hl=en">We</a> <a href="https://scholar.google.com/citations?user=4Y2R_IgAAAAJ&hl=en">are</a> <a href="https://scholar.google.com/citations?user=e22ajL0AAAAJ&hl=en">researchers</a> studying how these microenvironmental stresses affect tumor initiation and progression. In our <a href="https://www.nature.com/articles/s41556-022-01055-y">new study</a>, we found that the harsh microenvironments of the body can push certain cancer cells to overcome the stress of being isolated and make them more adept at initiating and forming new tumor colonies. Moreover, these cancer cells may adapt even better in the inhospitable and stressful conditions they encounter while trying to establish metastases in other areas of the body or after they are challenged by treatment with chemotherapy or surgery. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/Z9H2utcnBic?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The microenvironment of a cell can significantly influence its function.</span></figcaption>
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<h2>Cancer cells overcoming isolation stress</h2>
<p>We focused on <a href="https://doi.org/10.1001%2Fjama.2021.13027">pancreatic cancer</a>,
one of the most lethal cancers and one that is notoriously resistant to chemotherapy and often not curable with surgery. <a href="https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html">Almost 90%</a> of pancreatic patients will succumb to cancer recurrence or metastasis within five years after diagnosis. </p>
<p>We wanted to study how tumor formation is affected by what we call “<a href="https://www.nature.com/articles/s41556-022-01055-y">isolation stress</a>,” when cells are deprived of nutrients or oxygen supply because of poor blood vessel formation or because they cannot benefit from making contact with nearby cancer cells. To study how cancer cells respond to these situations, we recreated different forms of isolation stress in cell cultures, in mice and in patient samples by depriving them of oxygen and nutrients or by exposing them to chemotherapeutic drugs. We then measured which genes were turned on or off in pancreatic cancer cells.</p>
<p>We found that pancreatic cancer cells challenged with conditions that mimic isolation stress gain a new receptor on their surface that unstressed cancer cells don’t typically have: <a href="https://doi.org/10.1016/j.bbrc.2015.03.169">lysophosphatidic acid receptor 4, or LPAR4</a>, a protein involved in tumor progression. </p>
<p>When we forced the cancer cells to produce LPAR4 on their surfaces, we found that they were able to form new tumor colonies two to eight times faster than average cancer cells under isolation stress conditions. Also, preventing cancer cells from gaining LPAR4 when they were stressed reduced their ability to form tumor colonies by 80% to 95%. These findings suggest that the ability of cancer cells to gain LPAR4 when they are exposed to stress is both necessary and sufficient to promote tumor initiation.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of pancreatic cancer metastases arising from multiple different cell clusters" src="https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=458&fit=crop&dpr=1 600w, https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=458&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=458&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=575&fit=crop&dpr=1 754w, https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=575&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/504478/original/file-20230113-14-t3mmqi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=575&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Tumors contain multiple different types of cancer cells with unique genetic mutations. This image shows a variety of pancreatic cancer cell clusters, each of a different color, within a tumor.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/GXJM1U">Ravikanth Maddipati, Abramson Cancer Center at the Univ. of Pennsylvania, National Cancer Institute, National Institutes of Health via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>How does LPAR4 help build tumors?</h2>
<p>We also found that LPAR4 helps cancer cells achieve tumor initiation by giving them the ability to produce a web of macromolecules, or an <a href="https://doi.org/10.1038/s41467-020-18794-x">extracellular matrix network</a>, that provides them an adhesive foothold within an otherwise inhospitable environment. By producing a halo of their own matrix, cancer cells with LPAR4 can start building their own tumor-supporting niche that provides a refuge from isolation stresses.</p>
<p>We determined that a key component of this extracellular matrix is <a href="https://doi.org/10.3389/fonc.2020.00641">fibronectin</a>. When this protein binds to receptors called integrins on the surface of cells, it triggers a cascade of events that results in the expression of new genes promoting tumor initiation, stress tolerance and cancer progression. Eventually, other cancer cells are recruited into the fibronectin-rich matrix network, and a new satellite tumor colony starts to form. </p>
<p>Considering that tumor cells with LPAR4 can create their own tumor-supporting matrix on the fly, this suggests that LPAR4 may allow individual tumor cells to <a href="https://www.nature.com/articles/s41556-022-01055-y">overcome isolation stress conditions</a> and survive in the bloodstream, the lymphatic system involved in immune responses or distant organs as metastases.</p>
<p>Importantly, we found that isolation stress is not the only way to trigger LPAR4. Exposing pancreatic cancer cells to chemotherapy drugs, which are designed to impose stress upon cancer cells, also triggers an increase of LPAR4 on cancer cells. This finding might explain how such tumor cells could develop drug resistance.</p>
<h2>Keeping cancer cells stressed</h2>
<p>Understanding how to cut off the cascade of events that allows cancer cells to become stress-tolerant is important, because it provides a new area to explore for future treatments.</p>
<p>Our team is currently considering potential strategies to prevent cancer cells from utilizing the fibronectin matrix to gain stress tolerance, including drugs that can target the receptors that bind to fibronectin on the surface of tumor cells. One of these drugs, being developed by a company one of us co-founded, is poised to enter clinical trials soon. Other strategies include preventing cancer cells from gaining LPAR4 when they sense stress, or interfering with the signals that promote the generation of the fibronectin matrix.</p>
<p>For patients diagnosed with pancreatic cancer, there is a pressing need to discover how to improve the effectiveness of surgery or chemotherapy. Like combating weeds in your garden, this may require attacking the problem from multiple directions at once.</p><img src="https://counter.theconversation.com/content/197768/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Cheresh receives funding from the NIH. He is a co-founder of Alpha Beta Therapeutics, Inc., a company creating new therapeutics to treat cancer, for which he also has equity and serves on the scientific advisory board.</span></em></p><p class="fine-print"><em><span>Chengsheng Wu and Sara Weis 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>Some cancers are notoriously resistant to chemotherapy and not curable with surgery. Stopping tumors from adapting to the harsh microenvironments of the body could be a potential treatment avenue.Chengsheng Wu, Postdoctoral Scholar in Pathology, University of California, San DiegoDavid Cheresh, Professor of Pathology, University of California, San DiegoSara Weis, Senior Scientist in Pathology, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1921292022-11-01T11:48:39Z2022-11-01T11:48:39ZPancreatic cancer could be diagnosed up to three years earlier – new study<figure><img src="https://images.theconversation.com/files/491945/original/file-20221026-17-kmqrkd.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3840%2C2160&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/human-body-organs-anatomy-pancreas-3d-1007278972">Magic mine/Shutterstock</a></span></figcaption></figure><p>Every year, <a href="https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer">more than 10,000 people</a> in the UK are diagnosed with pancreatic cancer. Unfortunately, for most of those people, the disease is diagnosed too late to be cured. Less than 10% of people live five years following a diagnosis. </p>
<p>Pancreatic cancer is a silent disease. For many people, it has no symptoms until it is fairly advanced. Weight loss and increased blood glucose levels are known signs, but it has been unknown – until now – when these changes occur and to what extent. If we can better understand how and when these changes happen before pancreatic cancer diagnosis, we can use this knowledge to diagnose the disease earlier and potentially, in the future, save the lives of some of the people affected by this deadly disease. </p>
<p>In the largest study of its kind, <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275369">published in PLOS ONE</a>, researchers at the University of Surrey, together with researchers at the University of Oxford, investigated known signs of pancreatic cancer – weight loss, high blood sugar and diabetes – and looked at when they develop in relation to cancer. To undertake this research, we used a large dataset of more than 10 million people in England. The large size of the dataset was important to ensure that our findings represent the whole population. We extracted the information on pancreatic cancer diagnosis and the three attributes of interest and investigated how they change for people over time. </p>
<p>We compared the body-mass index (for weight loss) and HbA1c (for blood sugar) of nearly 9,000 people diagnosed with pancreatic cancer with those of a group of nearly 35,000 people who did not have the disease. We found that dramatic weight loss in people with pancreatic cancer started as early as two years before they received a diagnosis. </p>
<p>At the time of diagnosis, the average BMI of people with pancreatic cancer was nearly three units lower than people who did not have cancer. Raised glucose levels were detected even earlier – from three years before the diagnosis.</p>
<p>Our analysis revealed that weight loss in people with diabetes was associated with a higher risk of developing pancreatic cancer than in people without diabetes. And increasing glucose levels in people without diabetes was associated with a higher risk of pancreatic cancer than in people with diabetes.</p>
<p>The results suggest that unexplained weight loss, mainly in people with diabetes (but not exclusively) should be treated with suspicion. Also, increasing glucose levels, especially in people without weight gain, should be considered a potential red flag for pancreatic cancer. </p>
<p>These changes are important candidates for health checks that, if performed regularly, could help doctors identify people who may have undiagnosed pancreatic cancer. These people could be then referred to a hospital specialist for an abdominal scan to check for cancer. </p>
<p>The benefit of receiving an early diagnosis is that it reduces the chance of the cancer spreading and helps ensure patients are fit enough to withstand treatment.</p>
<h2>Where we go from here</h2>
<p>In our study, we looked at average rates. It would be important in the future to delve deeper into data and investigate individuals or groups of people who are more likely to experience weight loss and increased glucose levels. This approach could then focus on helping those people. </p>
<p>We are also looking to build this information into a more complex tool (an algorithm) that doctors could use. Using weight and glucose changes together, and potentially incorporating other key symptoms of pancreatic cancer (dark urine, light stool, yellow skin), is more powerful than looking at each of these measures separately. Such a tool could be a powerful way to improve early diagnosis and save lives.</p><img src="https://counter.theconversation.com/content/192129/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Agnieszka Lemanska receives funding from Pancreatic Cancer Action, Registered charity in England & Wales (1137689) and in Scotland (SCO49777).</span></em></p>Large new study identifies very early risk factors for pancreatic cancer.Agnieszka Lemanska, Senior Lecturer, Health Data Science, University of SurreyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1180202019-06-19T10:57:06Z2019-06-19T10:57:06ZNew research gives hope in the fight against pancreatic cancer<figure><img src="https://images.theconversation.com/files/277571/original/file-20190603-69071-kvx656.jpg?ixlib=rb-1.1.0&rect=0%2C31%2C7000%2C4516&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Pancreatic ductal adenocarcinoma (PDAC), the most common form of <a href="https://pancreapedia.org/reviews/pancreatic-ductal-adenocarcinoma">pancreatic cancer</a>, is the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396775/">third most common cause of death from cancer</a> in the United States and the fifth most common in the United Kingdom. Deaths from PDAC outnumber those from breast cancer despite the significant <a href="http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014">difference in incidence rates</a>.</p>
<p>Late diagnosis and ineffective treatments are the most important reasons for these bleak statistics.</p>
<p>PDAC is an aggressive and difficult malignancy to treat. Until now, the only chance for cure is the complete surgical removing of the tumor. Unfortunately, because PDAC is usually asymptomatic, by the time it is diagnosed 80% to 90% of patients have disease that is surgically incurable. PDAC thus remains one of the main biomedical challenges today due to its low survival rate – just <a href="http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014">5% of patients are still alive five years after diagnosis</a>.</p>
<p>However, in recent decades a number of studies have shed light on the molecular mechanisms responsible for the initiation and progression of PDAC. Our <a href="https://www.cell.com/cancer-cell/fulltext/S1535-6108%2819%2930111-4">recent research</a> has shown that progress toward a cure is possible.</p>
<h2>Ineffective treatments</h2>
<p>The molecular mechanisms responsible for pancreatic cancer are complex. This is why recent advances in <a href="https://theconversation.com/the-promise-of-personalized-medicine-is-not-for-everyone-100997">personalized medicine</a> and <a href="https://theconversation.com/2018-nobel-prize-in-physiology-or-medicine-a-turning-point-in-the-war-on-cancer-104191">immunotherapy</a> (which helps the immune system fight cancer) have failed to improve the treatment of pancreatic cancer. This is mainly due to two characteristics:</p>
<ul>
<li><p>95% of these tumors are caused by mutations in KRAS oncogenes. Oncogenes are genes that, once mutated, are capable of inducing the transformation of a normal cell into a cancerous cell. KRAS is a gene that <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2015/turning-off-broken-switch">acts as an on/off switch</a>. Normally, KRAS controls cell proliferation. When it is mutated, however, the cells start to grow uncontrollably and proliferate – a hallmark of cancer cells. So far, KRAS oncogenes have not been able to be targeted by drugs.</p></li>
<li><p>PDACs are surrounded by abundant fibrous connective tissue that <a href="https://www.medicinenet.com/script/main/art.asp?articlekey=7458">grows</a> around some tumor types. In the case of PDAC, this tissue forms a barrier that prevents cells that recognize and attack tumor cells, called <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cytotoxic-t-cell">cytotoxic T lymphocytes</a>, from reaching the inside of the tumor mass and killing its cells. This renders immunotherapy treatments useless.</p></li>
</ul>
<p>For these reasons, PDAC continues to be treated with drugs that destroy cancerous cells but can also destroy healthy ones. Options include <a href="https://en.wikipedia.org/wiki/Gemcitabine">Demcitabine</a>, approved in 1997, and Nab-paclitaxel, a new <a href="https://en.wikipedia.org/wiki/Paclitaxel">paclitaxel-based formulation</a>. Even if such a treatment is an option, it typically only extends the patients’ lives a few weeks, a marginal improvement at best.</p>
<p>In recent years, however, a number of studies have shed light regarding the molecular mechanisms responsible for the initiation and progression of PDAC.</p>
<p>Today we know that most of these tumors are caused by mutations in the KRAS oncogene. They lead to benign alterations that cause additional mutations in a range of <a href="https://www.cancer.org/cancer/cancer-causes/genetics/genes-and-cancer/oncogenes-tumor-suppressor-genes.html">tumor-suppressor genes</a>, which usually repair DNA mistakes, slow down cellular division or tell cells when to die. Mutated cells can grow out of control, and in this context progress to malignant PDAC.</p>
<p>While this process is relatively well known, it has not had an immediate impact on the development of new and more effective treatments.</p>
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Leer más:
<a href="https://theconversation.com/2018-nobel-prize-in-physiology-or-medicine-a-turning-point-in-the-war-on-cancer-104191">2018 Nobel Prize in Physiology or Medicine: a turning point in the war on cancer</a>
</strong>
</em>
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<h2>In search of new strategies</h2>
<p>Multiple strategies are currently being studied in an attempt to inhibit the growth of these tumors by blocking the growth of either the tumor cells or their surrounding “shielding” connective tissue. <a href="https://www.axa-research.org/fr/projet/mariano-barbacid">In our laboratory</a>, we focused on blocking the signaling pathways that mediate the oncogenic activity of the initiating KRAS oncogenes.</p>
<p>A decade ago, our lab decided to use genetically engineered mouse-tumor models capable of reproducing the natural history of human PDAC. We did this in order to analyze the therapeutic potential of the main components of the KRAS signaling pathways. These studies have unveiled the reason why the drugs tested so far have intolerable toxic effects, with mice dying within several weeks: they target some proteins that are essential for the dynamic state of equilibrium that is the condition of optimal functioning of the cells. This is called <a href="https://en.wikipedia.org/wiki/Homeostasis">normal homeostasis</a>.</p>
<p>These crucial proteins are mainly <a href="https://en.wikipedia.org/wiki/Kinase">kinases</a>, enzymes that are able to modify how other molecules function. They play a critical and complex role in regulating cellular signaling and orchestrate processes such as hormone response and cell division. These results might explain why the KRAS-signaling inhibitors tested so far have <a href="https://jamanetwork.com/journals/jama/issue/317/18">failed in clinical trials</a>. On the other hand, the removal of other signaling kinases did not have toxic side effects, but also had no impact on tumor development.</p>
<p>Of the more than 15 kinases involved in the transmission of signals from the KRAS oncogene, only three displayed significant therapeutic benefits without causing unacceptable side effects. These are: <a href="https://en.wikipedia.org/wiki/RAF_kinase">RAF1</a>, the <a href="https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor">epidermal growth factor receptor</a> (EGFR) and <a href="https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_4">CDK4</a>.</p>
<h2>It works! (in mice)</h2>
<p>In initial studies, we observed that the elimination (via genetic manipulation) of the expression of some of these three kinases prevented the onset of PDAC caused by the KRAS oncogene. However, its elimination in animals with advanced tumors had no significant therapeutic effects. These results caused us to question whether it would be possible to eliminate more than one kinase simultaneously without increasing the toxic effects.</p>
<p>As described in our recent work published in the journal <a href="https://www.sciencedirect.com/science/article/abs/pii/S1535610819301114"><em>Cancer Cell</em></a>, the elimination of RAF1 and EGFR expression induced the complete regression of advanced PDACs in 50% of the mice. <a href="https://www.ncbi.nlm.nih.gov/pubmed/30975481">We are currently studying</a> whether we can increase this by also eliminating CDK4.</p>
<p>The analysis of the pancreas of animals in which we were no longer able to observe tumors by imaging techniques revealed the complete absence of lesions in two of them. Two mice showed some abnormal ducts, probably residual scarring from the tumor. The others had tumor micro-masses of one-thousandth the size of the original tumor. The study of these revealed the presence of tumor cells, in which the expression of the two targets, EGFR and RAF1, had not been completely eliminated, a common technical problem in this type of study.</p>
<p>It is significant that these results were observed not only in mice. The inhibition of the expression of these two proteins in cells derived from nine out of ten human PDACs were also capable of blocking their proliferation <em>in vivo</em> when transplanted into immunosuppressed mice as well as <em>in vitro</em> cultures.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/278680/original/file-20190610-52741-btpg9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/278680/original/file-20190610-52741-btpg9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/278680/original/file-20190610-52741-btpg9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/278680/original/file-20190610-52741-btpg9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/278680/original/file-20190610-52741-btpg9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/278680/original/file-20190610-52741-btpg9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/278680/original/file-20190610-52741-btpg9.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">The elimination of RAF1 and EGFR expression induced the complete regression of advanced PDACs in half of the mice.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Lab_mouse_mg_3276.jpg">Rama/Wikimedia</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>What now?</h2>
<p>While these results have only been observed in a subset of mice for now, their importance lies in the fact that it is the first time that it has been possible to completely eliminate advanced PDAC tumors by eliminating a pharmacologically directed target.</p>
<p>These observations are clearly important for the development of treatments based on the inhibition of RAF1 and EGFR, but they only represent a first step on a long, hard road ahead.</p>
<p>First, it is important to identify the differences between the PDACs that respond to the combined elimination of RAF1 and EGFR and those that are resistant. As described in our work, the analysis of these two tumor types revealed that they are not active in the same way – more than 2,000 genes are expressed differently.</p>
<p>Identifying additional targets in resistant tumors that do not increase treatment toxicity is not going to be an easy task.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/wUJDAeU7J7E?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Mariano Barbacid speaks about precision medicine and cancer, Bose Memorial conference, 2018.</span></figcaption>
</figure>
<p>To continue our tests with genetically engineered mice, the immediate but no less difficult task is the development of specific RAF1 <a href="https://medical-dictionary.thefreedictionary.com/inhibitor">inhibitors</a>. Indeed, we only currently have potent drugs against the second target, EGFR. In principle, there are four possible approaches:</p>
<ul>
<li><p>Generate selective inhibitors for its kinase activity.</p></li>
<li><p>Generate inhibitors for its binding to the KRAS oncogene.</p></li>
<li><p>Generate inhibitors for its interaction with effector targets that transmit oncogenic signaling mediated by RAF1.</p></li>
<li><p>Degrade the RAF1 protein with drugs.</p></li>
</ul>
<p>Designing inhibitors of the RAF1 kinase activity would seem to be the most affordable option, given the experience of the pharmaceutical industry in <a href="https://www.ncbi.nlm.nih.gov/pubmed/26822576">designing this molecule type</a>.</p>
<p>The problem resides in the fact that there are two other kinases of the same family, ARAF and BRAF, whose catalytic centers (the “active core” of the enzymes) are nearly identical. RAF1 kinase inhibitors are also targeting these other kinases, which causes collateral damage. The ones tested to date have caused high toxicities and the clinical trials had to be stopped.</p>
<p>Continuing to develop effective molecules that are capable of blocking RAF1 activity in patients with PDAC will not be easy. It will surely take more time than we hope, but at least a road map has already been outlined that shows us how to keep moving forward.</p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/202296/original/file-20180117-53314-hzk3rx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/202296/original/file-20180117-53314-hzk3rx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=121&fit=crop&dpr=1 600w, https://images.theconversation.com/files/202296/original/file-20180117-53314-hzk3rx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=121&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/202296/original/file-20180117-53314-hzk3rx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=121&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/202296/original/file-20180117-53314-hzk3rx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=152&fit=crop&dpr=1 754w, https://images.theconversation.com/files/202296/original/file-20180117-53314-hzk3rx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=152&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/202296/original/file-20180117-53314-hzk3rx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=152&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
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</figure>
<p><em>Created in 2007 to help accelerate and share scientific knowledge on key societal issues, the AXA Research Fund has been supporting nearly 600 projects around the world conducted by researchers from 54 countries. To learn more about this AXA Research Fund project, please visit the <a href="https://www.axa-research.org/en/project/mariano-barbacid">dedicated page</a>.</em></p>
<hr>
<p><em>This article was translated from the original Spanish by Sara Crespo, <a href="https://www.calamoycran.com/">Calamo & Cran</a>.</em></p><img src="https://counter.theconversation.com/content/118020/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The grants received by Mariano Barbacid to carry out this work are cited in the related article published in the journal Cancer Cell. In addition, he owns shares in pharmaceutical companies, and also holds an endowed Chair in the AXA Research Fund.</span></em></p>Pancreatic cancer currently has one of the least optimistic prognosis, with just 5% of patients surviving five years after diagnosis. A recent study opens a door to hope.Mariano Barbacid, profesor e investigador AXA-CNIO de Oncología Molecular, Centro Nacional de Investigaciones Oncológicas CNIOLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1180322019-06-17T11:19:49Z2019-06-17T11:19:49ZThe Trebek effect: The benefits of well wishes<figure><img src="https://images.theconversation.com/files/279001/original/file-20190611-32327-1243lh8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Alex Trebek pictured in Pasadena, California on May 5, 2019.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/46th-Annual-Daytime-Emmy-Awards-Press-Room/c7df0a6d13b54bb39890cad64af43671/5/0">Richard Shotwell/Invision/AP</a></span></figcaption></figure><p>Long-time “Jeopardy!” host Alex Trebek announced in March that he had been diagnosed with stage 4 pancreatic cancer. Within days, he offered <a href="https://www.wfmynews2.com/video/news/alex-trebek-thanks-fans-for-their-well-wishes/83-89fec149-7fce-481d-aa13-1b2b087b97f2">thanks</a> to “the hundreds of thousands of people who have sent emails, texts, tweets, and cards wishing me well regarded my health.” Then last month, Trebek reported that his <a href="https://www.prevention.com/health/health-conditions/a26810982/alex-trebek-returns-jeopardy-after-pancreatic-cancer-diagnosis/">cancer</a> was in “near remission,” saying that his doctors “hadn’t seen this kind of positive results in their memory.”</p>
<p>Although the odds remain stacked against Trebek (advanced pancreatic cancer has a 3% 5-year survival rate), his experience raises an intriguing question: What are the benefits of such well wishes?</p>
<p>Greeting card industry <a href="https://www.greetingcard.org/industry-resources/industry-information/">statistics</a> amply demonstrate the relevance of the question to most Americans: We buy about 6.5 billion greeting cards a year, and while birthdays constitute the number one occasion, “Get Well” cards figure heavily in the mix.</p>
<h2>Benefits for recipients</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/279002/original/file-20190611-32347-1fo5vtn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279002/original/file-20190611-32347-1fo5vtn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279002/original/file-20190611-32347-1fo5vtn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279002/original/file-20190611-32347-1fo5vtn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279002/original/file-20190611-32347-1fo5vtn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279002/original/file-20190611-32347-1fo5vtn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279002/original/file-20190611-32347-1fo5vtn.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">Spending time with someone who is old, sick or restricted to home can break social isolation.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-happy-grandmother-giving-gift-her-502229566?src=pdX9FN7xRfZLMeMM7mFfTA-1-12">Andrey_Popov/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>The most immediately apparent benefits of well wishes accrue to recipients. When we are injured, sick or suffering, knowing that someone else is thinking about us can be a <a href="https://www.cancer.org/treatment/understanding-your-diagnosis/talking-about-cancer/when-someone-you-know-has-cancer.html">source of comfort</a>. It counteracts one of the <a href="http://www.gutenberg.org/files/23772/23772-h/23772-h.htm">worst aspects</a> of suffering – isolation. During periods of convalescence, we often miss school or take time off from work and other social activities, which leaves us feeling alone. Knowing that we are in <a href="https://www.health.harvard.edu/aging/5-ways-to-fight-loneliness-and-isolation">someone else’s thoughts</a> helps to counteract this. </p>
<p>When such well wishes are accompanied by offers of <a href="https://www.kansashealthsystem.com/care/specialties/palliative-care/resources/how-to-help">assistance</a>, they can help to solve everyday challenges. Co-workers might offer to assume work responsibilities so that a colleague can take the time needed to get better. Neighbors might offer to feed a convalescent’s pets, to deliver groceries or to help with household chores or self-care. Relatives might offer to stay with loved ones, or even bring them into their own homes to provide care.</p>
<p>Prayer offers perhaps the most dramatic opportunity to study the health benefits of well wishes. In studies of the efficacy of prayers for others, some <a href="https://journals.sagepub.com/doi/abs/10.1177/1049731506296170">studies</a> have shown small health benefits, while <a href="https://link.springer.com/article/10.1207/s15324796abm3201_3">others</a> have shown no effect. </p>
<p>As a practicing physician who teaches large numbers of medical students and residents, I believe that sharing well wishes benefits us in all sorts of ways that are not reflected in medical outcomes. For example, reaching out to others can reduce anxiety and fear, and connections formed during difficult times may persist for many years, even a lifetime.</p>
<h2>Benefits for well wishers</h2>
<p><a href="https://link.springer.com/article/10.1007/s10902-019-00100-2">Wishing others well</a> is also good for the person doing the well-wishing. For one thing, we cannot genuinely do so without shifting our attention away from ourselves. <a href="https://news.uchicago.edu/story/loneliness-contributes-self-centeredness-sake-self-preservation">Much unhappiness</a> can be traced to an excessive preoccupation with self, which for some can reach the point that we become curved in on ourselves. Thinking of others counteracts this. There is <a href="https://www.nature.com/articles/ncomms15964">neurological evidence</a> that acts of generosity make us feel less anxious and happier.</p>
<p>People who feel <a href="https://science.sciencemag.org/content/241/4865/540">disconnected</a> from others suffer health consequences worse than obesity, smoking and high blood pressure. By contrast, wishing others well helps us to recognize our <a href="http://ccare.stanford.edu/uncategorized/connectedness-health-the-science-of-social-connection-infographic/">interdependence</a>, thereby fostering a greater sense of connectedness. We tend to invest more of our own time and energy in others when we stop and contemplate how much our well-being – economic, social, psychological and spiritual – hinges on theirs.</p>
<p>Of course, there is a trap here that needs to be recognized and avoided. We cannot genuinely wish others well if we are doing it for our own sake. Merely to appear to others to have their best interests at heart while really pursuing our own is but a form of deception, only compounding the adverse effects of self-centeredness and isolation. To realize real benefits from caring for others, we must genuinely care for them.</p>
<h2>Benefits for all</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/279003/original/file-20190611-32342-68c63p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279003/original/file-20190611-32342-68c63p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279003/original/file-20190611-32342-68c63p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279003/original/file-20190611-32342-68c63p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279003/original/file-20190611-32342-68c63p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279003/original/file-20190611-32342-68c63p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279003/original/file-20190611-32342-68c63p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Supporting one another through difficult times can be good for both parties.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-two-hands-joining-together-symbolizing-546359626?src=499q8T-GNsierDAqocZRjw-1-22">BRAIN2HANDS/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>It is so important to care for others that we should do it, at least in some cases, even when it redounds to our detriment. For example, marriage, parenting and friendship involve sacrifices. Sometimes we set aside our own good entirely to tend to the needs of another. While we may not benefit directly from such sacrifices, we do help to build larger wholes – relationships and communities – of which we are all a part. We make the world a better place.</p>
<p>The need to foster mutual care has perhaps never been greater. When <a href="https://journals.sagepub.com/doi/abs/10.1177/000312240607100301">Americans</a> were asked in 1985 to say how many people they were close to, the typical response was three. By 2004, this number had dropped to zero. Over one-quarter of us reported that we have no one we consider a close friend.</p>
<p>I knew a physician who once met a patient with end-stage skin cancer in the emergency department. When it became clear that the patient had no place to go and no one to care for her, the physician, who had once been a nun, brought the patient into her own home, where she, her husband and their two sons cared for the woman around the clock during the last few weeks of her life. When such stories are shared, they can inspire our own resolve to do more to care more for those in need.</p>
<p>The recent outpouring of well wishes for a television game show host – a stranger to most who reached out to him – offers an important insight into what makes families, friendships and communities thrive. Connectedness and its benefits are not something we should take for granted. Whether in the form of a simple text message or greeting card – or better yet, a phone call or a visit – letting someone who is hurting know that we care can make a big difference for all.</p>
<p>[ <em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/118032/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Gunderman 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>Alex Trebek raised an interesting question when he thanked well-wishers for supporting him in his fight against pancreatic cancer: Do prayers and good thoughts really have a medical effect?Richard Gunderman, Chancellor's Professor of Medicine, Liberal Arts, and Philanthropy, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1181002019-05-31T11:11:11Z2019-05-31T11:11:11ZPancreatic cancer specialist explains challenges of the disease and treatment advances<p>With <a href="https://www.cnn.com/2019/05/29/entertainment/alex-trebek-cancer-update/index.html">Alex Trebek’s recent announcement</a> that his pancreatic cancer is in remission, many people have wondered if this difficult cancer is now easier to treat. Pancreatic cancer remains a major cancer killer, but advances are happening.</p>
<p>As a medical oncologist who specializes in treating and studying pancreatic cancer, I’ll try to provide insights, including some from the American Society of Clinical Oncology (ASCO) meeting now underway. </p>
<h2>Pancreatic cancer and its toll</h2>
<p>We oncologists, or cancer specialists, call the disease “pancreatic ductal adenocarcinoma,” or PDAC. It is a leading cause of cancer-related death, currently ranking as the seventh leading cause of cancer deaths globally and the third in the U.S.</p>
<p>Often diagnosed at an advanced stage, pancreatic cancer has a low survival rate of <a href="https://www.cancer.net/cancer-types/pancreatic-cancer/statistics">9%</a> or less. </p>
<p>Although cancers are usually classified as stages from I to IV, in PDAC we have found that a different system which corresponds to how we actually treat these tumors is more useful. The earliest stage is when the cancer is determined to be surgically resectable, that is, removable through surgery. About 15% of patients’ tumors are found at this stage.</p>
<p>About 40% of patients’ tumors have further progressed to where they attach themselves to or encompass local structures. This is further broken down into borderline tumors that, although technically removable, require chemotherapy and radiation therapy prior to surgery to ensure their complete removal. </p>
<p>Locally advanced tumors cannot be surgically removed in most cases as they completely surround critical blood vessels or infiltrate into adjoining critical organs.</p>
<p>The remainder of pancreatic cancers are already metastatic - they have already spread to distant areas. Nearly all long-term pancreatic cancer survivors are diagnosed when their cancer is, or can be made, surgically removable. Contrarily, because of the limited number of treatment options, and inherent resistance to treatment, exceedingly few five-year survivors present with Stage IV disease.</p>
<h2>Lack of screening an impediment</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/277277/original/file-20190530-69059-o11rlb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/277277/original/file-20190530-69059-o11rlb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=313&fit=crop&dpr=1 600w, https://images.theconversation.com/files/277277/original/file-20190530-69059-o11rlb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=313&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/277277/original/file-20190530-69059-o11rlb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=313&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/277277/original/file-20190530-69059-o11rlb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=393&fit=crop&dpr=1 754w, https://images.theconversation.com/files/277277/original/file-20190530-69059-o11rlb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=393&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/277277/original/file-20190530-69059-o11rlb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=393&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The pancreas is located in the abdomen, making diagnosis of pancreatic cancer difficult.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Pancreas_Location.png">Bruce Blaus/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>A key challenge in treating pancreatic cancer is the lack of good screening techniques to identify such cancers in their earliest stages, as the pancreas lies in an anatomically unfavorable position for early diagnosis, toward the back of the abdomen.</p>
<p>By the time the diagnosis of pancreatic adenocarcinoma is suspected, typically by symptoms such as <a href="https://www.pancan.org/news/7-pancreatic-cancer-symptoms-and-signs-you-should-know/">jaundice, pain and weight loss</a>, the tumor has already grown to a point where surgical removal is difficult. Critical vascular and other structures hamper surgical excision. Or, it has grown to a point where it has spread to distant sites.</p>
<p>Additionally, well before a physician diagnoses a patient’s pancreatic cancer, there is often what we call microscopic metastatic disease. This means that cancer cells are already hiding in other parts of the body. Preoperative and postoperative chemotherapy and radiation are used to try to kill such stealth tumor cells. However, despite these treatments, most patients whose tumors are surgically removed will die of recurrence resulting from these remaining tumor cells.</p>
<h2>Chemo, and more chemo</h2>
<p>Once spread to other organs either at presentation or in relapse, PDAC is not curable except in rare circumstances. However, treatment of patients with metastatic disease can yield benefits in terms of overall survival and a quality of life.</p>
<p>Historically, standard chemotherapy for these patients has included one or two drugs, but newer chemotherapy combinations are being used in patients who can tolerate more aggressive systemic therapy. Some of these may be used <a href="https://doi.org/10.1056/NEJMoa1011923">in combination</a>.</p>
<p>In particularly fit patients, another sequence of chemotherapy after the first drugs yields continued responses, but unfortunately, rarely leads to a complete remission of all disease.</p>
<p>Up to two-thirds of patients will gain benefit from these sequential chemotherapy treatments, resulting in the halt of their disease growth, or have a partial decrease in the amount of their tumor. In the past, the one-year survival of patients with metastatic disease was 15-20%. New combinations given sequentially can raise the one-year survival rate to about 50%.</p>
<p>Inevitably, due to the development of resistance in a patient’s tumor to chemotherapy, as well as toxicities of treatment, even those who initially respond succumb to disease progression. By five years after diagnosis, patient survival with metastatic disease is less than 3%. </p>
<p>Also, PDAC is mostly diagnosed in older individuals with concomitant medical issues, and this limits treatment. Chemotherapy tolerance and survival is poorer in many individuals, although treatment can still yield benefits in terms of quality of life.</p>
<h2>Hope on the horizon?</h2>
<p>Recent <a href="https://theconversation.com/global-study-of-pancreatic-cancer-offers-possible-insights-into-treatment-and-early-detection-113254">advances in our molecular understanding</a> of PDAC have yielded new treatment paradigms with the hope of improving these results. We know that some people with pancreatic cysts, or pockets of fluid within the pancreas, are at increased risk of developing pancreatic cancer. Yet distinguishing potentially cancerous cysts from benign, or non-cancerous, ones has been difficult. <a href="https://theconversation.com/global-study-of-pancreatic-cancer-offers-possible-insights-into-treatment-and-early-detection-113254">Recent molecular techniques</a> have been developed to help stratify the risks of developing cancer in these cysts, enabling their surgical removal during their earliest and most curable stage.</p>
<p>Similarly, recent research has yielded a better understanding of the molecular changes that can lead to the development of pancreatic cancer. Studies have demonstrated that up to 10% of pancreatic cancer patients have DNA alterations that can be identified in their blood, that are potentially clinically useful, and that may also <a href="http://doi.org/10.1002/cncr.31628">raise the risk</a> to family members who have those same DNA changes for developing PDAC. Clinical treatment strategies are being developed to not only direct treatment at these specific changes, but also to develop screening techniques to identify PDAC in similarly affected family members at an earlier and more treatable stage.</p>
<p>For example, patients who harbor a <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/germline-dna">germline</a> change in the <a href="https://ghr.nlm.nih.gov/gene/BRCA2">BRCA2 gene</a> are at higher risk of developing pancreatic cancer as well as breast, ovarian, prostate and other cancers. A class of drugs called <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/parp-inhibitor">PARP inhibitors</a>, which have been utilized in treating breast and ovarian cancers that are dependent on BRCA2, have been recently shown to offer a survival benefit in pancreatic patients whose tumors harbor the same BRCA2 gene mutations.</p>
<p>Evaluation of <a href="http://doi.org/10.1053/j.gastro.2019.02.037%5D(http://doi.org/10.1053/j.gastro.2019.02.037">pancreatic cancer DNA</a> has yielded insights into a number of altered genes that are yielding better and more directed therapies. For example, researchers have found targetable alterations in the <a href="https://ghr.nlm.nih.gov/gene/ALK">ALK</a> and <a href="https://ghr.nlm.nih.gov/gene/NTRK1">NTRK</a> genes in tumors of particular pancreatic cancer patients. Identification of these altered genes in patient’s tumors allows for much better tolerated and effective treatments directed at these tumor-causing genes. As a result, it is now considered standard of care to offer germline and tissue DNA analysis to all pancreatic cancer patients to identify such actionable gene defects.</p>
<p><a href="https://www.cancer.gov/about-cancer/treatment/types/immunotherapy">Immunotherapy</a>, which has been transforming treatment in a host of other cancers, may one day be effective. Although no large randomized trial has yet proven the efficacy of immune therapies in pancreatic cancer, <a href="https://www.ascopost.com/News/59890">data published in April 2019</a> utilizing a combination of drugs have yielded hopeful preliminary results.</p>
<p>Other clinical studies targeting the unique metabolism of pancreatic cancers or the surrounding tissue are underway as well. Clearly, given the otherwise poor survival statistics for pancreatic cancer using our classical therapy options, the future of pancreatic cancer treatment lies in the development of novel agents to supplant or be added to current chemotherapy regimens.</p>
<p>We oncologists are hopeful for all patients diagnosed with this difficult disease, and we wish the very best to Alex Trebek in his continued fight.</p><img src="https://counter.theconversation.com/content/118100/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nathan Bahary receives funding from the National Institutes of Health and the National Cancer Institute for ongoing research. </span></em></p>Alex Trebek announced this week that his pancreatic cancer is in remission. A pancreatic cancer specialist explains the difficulties of the disease as well as new treatment advances.Nathan Bahary, Associate Professor of Medicine, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1132542019-03-18T10:46:25Z2019-03-18T10:46:25ZGlobal study of pancreatic cancer offers possible insights into treatment and early detection<figure><img src="https://images.theconversation.com/files/264013/original/file-20190314-28499-192j19c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Alex Trebek shown in 2006.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Alex-Trebek-Cancer/a8dffa63d0e141b6b57ea3db87ccb177/1/0">Reed Saxon/AP Photo</a></span></figcaption></figure><p>When “Jeopardy!” <a href="http://www.j-archive.com/showgame.php?game_number=7059">episode 7059</a> aired on April 30, 2015, the category was “The Human Body,” the price was $2,000, and the clue was “This gland’s main duct, the <a href="https://www.britannica.com/science/duct-of-Wirsung">duct of Wirsung</a>, collects its juices & empties into the <a href="https://www.britannica.com/science/duodenum">duodenum</a>.” </p>
<p>The question was “What is the pancreas?” Unbeknownst to <a href="https://www.prevention.com/health/health-conditions/a26810982/alex-trebek-returns-jeopardy-after-pancreatic-cancer-diagnosis/">Alex Trebek</a>, the show’s beloved host, the cells that line the duct of his pancreas would develop into pancreatic cancer, or pancreatic ductal adenocarcinoma. Trebek announced on March 6, 2019 that he has <a href="https://www.cnn.com/2019/03/06/entertainment/alex-trebek-pancreatic-cancer/index.html">pancreatic cancer</a>, but that he will fight the disease and keep hosting the show. And in fact, he was <a href="https://abcnews.go.com/WNT/video/alex-trebek-returns-jeopardy-sharing-cancer-diagnosis-61666555">back at work</a> March 12.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/7cInGyxCY9k?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Alex Trebek announces he has pancreatic cancer.</span></figcaption>
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<p>“Truth told, I have to because under the terms of my contract, <a href="https://www.cnn.com/2019/03/06/entertainment/alex-trebek-pancreatic-cancer/index.html">I have to host ‘Jeopardy’ for three more years</a>,” he said jokingly. “So help me. Keep the faith, and we’ll win. We’ll get it done.”</p>
<p>I am a surgical and molecular pathologist at the University of Pittsburgh Medical Center and routinely evaluate patients with pancreatic cancer. As a pathologist, I establish the diagnosis and evaluate the genetics of pancreatic cancer to improve early detection and treatment of pancreatic cancer.</p>
<p>Although Trebek’s recovery is still unknown, researchers are trying to develop diagnostic tests that will let people know earlier that they have this form of cancer. A <a href="https://doi.org/10.1053/j.gastro.2019.02.037">study</a> my colleagues and I recently published identified genetic differences in patients that might make current chemotherapies more effective. </p>
<h2>Hard to detect, hard to treat</h2>
<p>Each day in the U. S., an estimated 155 Americans will be diagnosed with pancreatic cancer and an estimated 125 Americans will die of pancreatic cancer. About <a href="https://www.cancer.net/cancer-types/pancreatic-cancer/statistics">55,440 will be diagnosed</a> this year. </p>
<p>Within the first year of diagnosis, 74 percent of patients with pancreatic cancer will die from this dismal disease and 90 percent of patients will die within five years of their diagnosis. </p>
<p>What makes pancreatic cancer so deadly is that it is often found late in its disease course, as in the case of Trebek. Hence, time is of the essence when it comes to treatment. </p>
<p>Current options for most patients are chemotherapy, radiation and, for a minority, surgery. But every pancreatic cancer is different, and therefore it requires a personalized approach, such as understanding the different genetic changes occurring in each patient’s pancreatic cancer. </p>
<p>At the University of Pittsburgh Medical Center (UPMC), we try to genetically profile every patient with pancreatic cancer to define their best course of treatment. While pancreatic cancer is so dire, there are genetic changes that can be targeted with currently available medications, and it’s important to identify them sooner than later. </p>
<p>But, in order for us to accomplish this, we have to know what genomic changes to look for in pancreatic cancer. Hence, in collaboration with <a href="https://www.foundationmedicine.com">Foundation Medicine</a>, my research team and I genetically profiled 3,594 patients from all over the world. We were looking for genetic changes that are linked to known therapeutic regimens for not only pancreatic cancer, but all cancer types. This approach has had some success with other cancer types. For example, a genetic mutation was found in some types of lung cancer that was sensitive to immunotherapy drugs such as <a href="https://immuno-oncologynews.com/keytruda-pembrolizumab/">Keytruda</a>. That drug had first gained FDA approval for treatment of melanoma. </p>
<p>With such a large and diverse patient population, it is not surprising that there were a number of key findings from our study.</p>
<h2>Mutations that could be targeted</h2>
<p>First, we found that <a href="https://doi.org/10.1053/j.gastro.2019.02.037">17 percent of pancreatic cancers contained genetic mutations</a> that may be susceptible to currently available anti-cancer therapy. While many of the genetic mutations we detected in pancreatic cancer have been described previously, we also identified genetic changes that were reported in other cancer types, but never described in pancreatic cancer. Moreover, these mutations are known to be targetable with existing drug regimens and are potentially therapeutic for patients with pancreatic cancer as well.</p>
<p>Second, we discovered a significant number of pancreatic cancer patients harbored mutations in their <a href="https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/germline-dna">germline DNA</a>, or in other words, a genetic change that has been incorporated into every cell in their body. </p>
<p>Previous studies have shown that 10 percent of patients with pancreatic cancer report a family history of the disease, and a subset have been linked to specific genomic alterations. For example, germline alterations in the genes BRCA1 and BRCA2, which are known to be associated with hereditary breast and ovarian cancer, have also been linked to pancreatic cancer. </p>
<p>We were not surprised that these genes were frequently mutated among patients within our study and additional genes related to them were also found to be altered. This information paves the way for improved germline testing for patients that may have a history of pancreatic cancer with implications for their loved ones.</p>
<p>Our last bit of insight came from looking at the genomic changes in pancreatic cyst fluid. About 15 percent of pancreatic cancers are known to arise from pancreatic cysts, or fluid collections within the pancreas. Pancreatic cysts are often identified on routine abdominal imaging and, therefore, amenable to early detection. Because early detection of pancreatic cancer is an important cornerstone to improving patient survival, my team examined those pancreatic cancers arising from pancreatic cysts. </p>
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<img alt="" src="https://images.theconversation.com/files/264177/original/file-20190315-28492-yxiq92.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/264177/original/file-20190315-28492-yxiq92.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/264177/original/file-20190315-28492-yxiq92.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/264177/original/file-20190315-28492-yxiq92.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/264177/original/file-20190315-28492-yxiq92.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/264177/original/file-20190315-28492-yxiq92.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/264177/original/file-20190315-28492-yxiq92.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">
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<span class="caption">A pancreatic cyst, marked by an arrow, as shown on an MRI. Only a small percentage of such cysts lead to cancer.</span>
<span class="attribution"><span class="source">University of Pittsburgh Medical Center</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Pancreatic cysts, however, are very common in the U.S. population. In fact, 1 to 2 percent of Americans who undergo an abdominal scan are found to have a pancreatic cyst. Certainly, not all pancreatic cysts will progress to pancreatic cancer and, therefore, tests to detect a pancreatic cancer arising within a pancreatic cyst early are needed. </p>
<p>In 2017, our team at UPMC reported the creation and validation of a clinically available test to evaluate patients with pancreatic cysts called <a href="https://mgp.upmc.com/Applications/mgp/Home/Test/PanSeq_details">PancreaSeq</a>. PancreaSeq evaluates the genetic changes in pancreatic cyst fluid to identify those cysts that are likely to transform into pancreatic cancer. It is used by several institutions throughout the U.S. </p>
<p>Among the 3,594 pancreatic cancers profiled for our recent study, we identified key genetic alterations among pancreatic cancers arising from pancreatic cysts that could be incorporated into PancreaSeq and improve its ability to detect pancreatic cancer early.</p>
<p>We believe that our study provides a compendium of known genetic alterations for pancreatic cancer that may serve as a clinical resource to not only guide future treatment for patients undergoing targeted genetic profiling, but familial pancreatic cancer testing and early detection.</p><img src="https://counter.theconversation.com/content/113254/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Aatur Singhi receives funding from the Pancreatic Cancer Action Network, the Sky Foundation, and the National Cancer Institute Early Detection Research Network. </span></em></p>Pancreatic cancer has historically had among the lowest survival rates of any type of cancer. A recent study that looked at genomic changes reveals some possible clues.Aatur Singhi, Professor of Anatomy and Pathology, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/902212018-01-18T19:17:24Z2018-01-18T19:17:24ZA new blood test can detect eight different cancers in their early stages<figure><img src="https://images.theconversation.com/files/202371/original/file-20180117-53310-9zjg6j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Liquid biopsy is less invasive than standard biopsy, where a needle is put into a solid tumour to confirm a cancer diagnosis.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Researchers have <a href="http://science.sciencemag.org/content/early/2018/01/17/science.aar3247">developed a blood test</a> that can detect the presence of eight common cancers. Called CancerSEEK, the blood test detects tiny amounts of DNA and proteins released into the blood stream from cancer cells. This can then indicate the presence of ovarian, liver, stomach, pancreatic, oesophageal, bowel, lung or breast cancers.</p>
<p>Known as a liquid biopsy, the test is distinctly different to a standard biopsy, where a needle is put into a solid tumour to confirm a cancer diagnosis. CancerSEEK, is also far less invasive. It can be performed without even knowing a cancer is present, and therefore allow for early diagnosis and more chance of a cure. </p>
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Read more:
<a href="https://theconversation.com/interactive-body-map-what-really-gives-you-cancer-52427">Interactive body map: what really gives you cancer?</a>
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<p>The test has been shown to reliably detect early stage and curable cancers. It has also been found to rarely be positive in people who don’t have cancer. This prevents significant anxiety and further invasive tests for those who don’t need them. </p>
<p>Several cancers can be screened for at once, and the test can be performed at the same time as routine blood tests, such as a cholesterol check. But the test is still some years away from being used in the clinic.</p>
<h2>How the test works</h2>
<p>Often long before causing any symptoms, even very small tumours will begin to release minute amounts of mutated DNA and abnormal proteins into blood. While DNA and proteins are also released from normal cells, the DNA and proteins from cancer cells are unique, containing multiple changes not present in normal cells. </p>
<p>The newly developed blood-based cancer DNA test is exquisitely sensitive, accurately detecting one mutated fragment of DNA among 10,000 normal DNA fragments, literally “finding the needle in the haystack”.</p>
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<a href="https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/202381/original/file-20180118-114739-vxgc1e.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>
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<span class="caption">Tumours release mutated DNA and abnormal proteins into blood.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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<p>We used CancerSEEK in just over 1,000 people with different types of early stage cancers. It was shown to accurately detect the cancer, including in 70% or more of pancreas, ovary, liver, stomach and esophageal cancers. For each of these tumour types there are currently no screening tests available – blood based or otherwise. </p>
<p>Along with cancer detection, the blood test accurately predicted what type of cancer it was in 83% of cases. </p>
<p>Published in the journal <a href="http://science.sciencemag.org/content/early/2018/01/17/science.aar3247">Science</a>, the research was led by a team from John Hopkins University, with collaboration from Australian scientists at the Walter and Eliza Hall Institute. </p>
<h2>Why it’s important</h2>
<p>Steady progress continues to be made in the treatment of advanced cancers, including major gains in life expectancy. But this can come at significant physical and financial cost. Early diagnosis remains the key to avoiding the potentially devastating impact of many cancer treatments and to reducing cancer deaths. </p>
<p>However, where there are proven screening tests that lead to earlier diagnosis and better outcomes, such as colonoscopy screening for bowel cancer, these are typically unpleasant. They also have associated risks, only screen for one cancer at a time and population uptake is often poor. And for many major tumour types there are currently no effective screening tests.</p>
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Read more:
<a href="https://theconversation.com/can-we-use-a-simple-blood-test-to-detect-cancer-63183">Can we use a simple blood test to detect cancer?</a>
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</em>
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<p>There are characteristic patterns of mutations and altered proteins that differ among cancer types. So CancerSEEK can not only detect that there is a cancer somewhere in the body but can also suggest where to start looking. </p>
<p>For example, if the pattern suggests a bowel cancer, then a colonoscopy is a logical next step. When blood samples were taken from over 800 apparently healthy controls, less than 1% scored a positive test. This means the test is rarely positive for people who don’t have cancer, thereby reducing the problem of overdiagnosis.</p>
<p>Overall, these results appear to be in stark contrast to previously developed blood-based tests for cancer screening. Currently the only widely used one of is the prostate specific antigen (PSA) test for prostate cancer. This has multiple limitations and some would argue the jury is still out on whether PSA based testing does more good than harm. </p>
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Read more:
<a href="https://theconversation.com/four-reasons-i-wont-have-a-prostate-cancer-blood-test-35085">Four reasons I won't have a prostate cancer blood test</a>
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<h2>What next?</h2>
<p>Large trials are now underway in the US, with CancerSEEK testing being offered to thousands of healthy people. Cancer incidence and outcomes in these people will be compared to a control group who do not have testing. Study results will be available in the next three to five years.</p><img src="https://counter.theconversation.com/content/90221/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Gibbs received funding from NHMRC that supported some of the research described. </span></em></p>There are currently few effective and non-invasive methods to screen for early stages of cancer. But scientists have now developed a new blood test that promises to detect eight different cancers.Peter Gibbs, Professor and Laboratory Head, Walter and Eliza Hall InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/832452017-08-31T10:15:34Z2017-08-31T10:15:34ZNew app detects pancreatic cancer in the early stages<figure><img src="https://images.theconversation.com/files/183978/original/file-20170830-30776-sbutmi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">BiliScreen, used for detecting signs of jaundice in a person's eye.</span> <span class="attribution"><a class="source" href="https://www.eurekalert.org/multimedia/pub/149069.php?from=368931">Dennis Wise/University of Washington</a></span></figcaption></figure><p>Pancreatic cancer is one of the most deadly cancers. It has a five-year survival of <a href="http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer">just 3%</a>, and a ten-year survival of <a href="http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer">less than 1%</a>. The prime reason for these depressing figures is that the disease is very difficult to detect in the early stages. By the time it is detected, it is often incurable. But help may be at hand.</p>
<p>Researchers at the University of Washington have developed an app called BiliScreen that can detect pancreatic cancer at the early stages. A build-up of bilirubin – which causes the eyes and skin to yellow – is one of the early indicators of the disease. The app calculates the amount of bilirubin in the whites of a person’s eyes. The user takes a selfie and a machine-learning algorithm – a type of artificial intelligence – performs the diagnosis.</p>
<p>Bilirubin is produced when the liver breaks down old red blood cells. Jaundice, the yellow discoloration of the skin and sclera (the white part of the eyes), results from an excess of this substance. This discolouration is only visible when jaundice is quite severe. However, BiliScreen produces an estimate of a person’s bilirubin level even at levels too low to be detected by the naked eye. </p>
<p>At the moment, the user of the app needs to use a special box (similar to a VR headset) to block out light from other sources, but the makers of the app hope that future versions won’t need this additional equipment. </p>
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<p>A <a href="https://ubicomplab.cs.washington.edu/pdfs/biliscreen.pdf">clinical study</a> of BiliScreen, involving 70 participants, found that the app has a high sensitivity (90%). This is the ability of a test to correctly identify people with a disease. In this case, 90% of the people with abnormally elevated bilirubin levels were correctly identified. The app also had high specificity, meaning there were few “false positives” – healthy people wrongly identified as having a disease. </p>
<p>BiliScreen can also be used to detect other reasons for jaundice, such as <a href="http://www.nhs.uk/Conditions/Hepatitis/Pages/Introduction.aspx">hepatitis</a> and <a href="http://www.nhs.uk/conditions/Gilbertssyndrome/Pages/Introduction.aspx">Gilbert’s syndrome</a>, a common, harmless liver condition in which the liver doesn’t properly process bilirubin. </p>
<p>An earlier version of the app – called <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=BiliCam">BiliCam</a> – was used to detect jaundice in newborns by taking snapshots of their skin. </p>
<h2>Not a doctor</h2>
<p>BiliScreen joins a growing list of apps used for diagnosis, including other cancers. For example, there are a number of apps that screen for skin cancer. Some of these apps use fractal geometry to assess the shape of moles. </p>
<p>A scientific <a href="http://onlinelibrary.wiley.com/doi/10.1111/bjd.13665/full">review of these melanoma-detecting apps</a> found that some of them have high sensitivity and specificity (73% and 83% respectively). However, the study found that a diagnosis given by a dermatologist and pathologist, if a biopsy is needed, gives a higher sensitivity and specificity – 88% and 97% respectively.</p>
<p>Although diagnostic apps will never take the place of doctors, they can act as useful early detectors of disease. And, in the case of BiliScreen, they are more convenient and less invasive than the usual test for jaundice, which involves a trip to the doctor and a blood draw. But whether people will be disciplined enough to regularly use a growing range of apps to screen for diseases, when they’re feeling in the peak of health, remains to be seen.</p><img src="https://counter.theconversation.com/content/83245/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Pinar Uysal-Onganer 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>An app could help diagnose one of the most deadly cancers at the early stages using eye-scanning technology.Pinar Uysal-Onganer, Lecturer in Molecular Biology, University of WestminsterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/764722017-05-04T14:34:47Z2017-05-04T14:34:47ZCould taking vitamins in huge doses produce a health miracle after all?<figure><img src="https://images.theconversation.com/files/166628/original/file-20170425-27254-154fvs3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Back in business?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/human-raised-hands-mercy-right-trust-324636710?src=O9QKs31qre_88fzIbXgY1Q-1-8">CHOATphotographer</a></span></figcaption></figure><p>For decades, some people have embraced the idea that there might be major health benefits from taking vitamins in quantities well beyond the <a href="http://www.nhs.uk/Conditions/vitamins-minerals/Pages/vitamins-minerals.aspx">recommended</a> daily requirement. The concept was very popular for a while <a href="http://content.time.com/time/covers/0,16641,19920406,00.html">in the media</a>, but research findings to the contrary gradually made it virtually untouchable for scientists. </p>
<p>Yet it is now making a sort of comeback, thanks partly to <a href="http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30062-4">new findings</a> demonstrating that high doses of vitamin C can treat cancer. As we shall see, however, there are some important caveats here – as well as obstacles to unlocking different potential health benefits from other vitamin treatments. This is a cautionary tale of the dangers of black and white thinking, and how things are rarely as simple as they can be made to appear. </p>
<p>It is about a hundred years since vitamins first came to prominence. <a href="http://www.rsc.org/Education/Teachers/Resources/Contemporary/student/pop_casimir.html">Described</a> in the early days as “vital-amines”, important for “vitality” (life), the public’s knowledge was originally based on solid science. But <a href="http://www.alternet.org/personal-health/how-vitamin-industry-tricks-people-shelling-out-millions-bunk-products">from the 1940s</a>, the information <a href="https://www.quackwatch.org/01QuackeryRelatedTopics/spotquack.html">became conflicted</a> as food manufacturers and later the dietary supplements industry took over much of the education on nutrition. </p>
<p>One example of this advice that has endured to the present day is the idea that we need to bolster our diets with extra vitamins and minerals. This has been phenomenally profitable for everyone in this business, from producers of breakfast cereals to vitamin pills. The dietary supplements sector <a href="https://www.mordorintelligence.com/industry-reports/global-nutraceuticals-market-industry">was worth</a> US$205 billion (£160 billion) last year and <a href="https://globenewswire.com/news-release/2016/07/18/856668/0/en/Dietary-Supplements-Market-Size-Is-Projected-To-Reach-278-02-Billion-By-2024-Demand-In-Food-Beverage-Sector-Grand-View-Research-Inc.html">is predicted</a> to rise to nearly US$280 billion by 2024. </p>
<h2>The rollercoaster remedy</h2>
<p>The idea of miraculous healing properties from taking vitamins in much larger quantities has long been part of this line of thinking – largely thanks to a leading American scientist named Linus Pauling. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=849&fit=crop&dpr=1 600w, https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=849&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=849&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1066&fit=crop&dpr=1 754w, https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1066&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/167362/original/file-20170501-17316-112xzlt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1066&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">Linus Pauling in 1962.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Linus_Pauling_1962.jpg#/media/File:Linus_Pauling_1962.jpg">Wikimedia</a></span>
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<p>I have written <a href="https://theconversation.com/taking-high-doses-of-vitamins-can-do-more-harm-than-good-15388">previously</a> in The Conversation about how Pauling, a double Nobel prize winner in chemistry and peace, became singularly committed in the 1960s and 1970s <a href="https://www.quackwatch.com/01QuackeryRelatedTopics/pauling.html">to the idea</a> that megadoses of vitamin C could treat diseases from the common cold to cancer. Pauling pushed these claims through a combination of exaggeration and selecting only studies showing positive effects – with a helping hand from the manufacturers. The story is described very well <a href="https://www.theatlantic.com/health/archive/2013/07/the-vitamin-myth-why-we-think-we-need-supplements/277947/">here</a>. </p>
<p>Other scientists <a href="http://www.nejm.org/doi/full/10.1056/NEJM197909273011303">began debunking</a> these claims as far back as the late 1970s, <a href="https://www.theatlantic.com/health/archive/2013/07/the-vitamin-myth-why-we-think-we-need-supplements/277947/">demonstrating</a> not only that Pauling was wrong but also that taking oral vitamin or mineral supplements can often do more harm than good – including in the treatment of <a href="https://www.ncbi.nlm.nih.gov/pubmed/24266867">certain cancers</a>. It soon reached the point that any idea of benefits from vitamin megadoses was considered dubious within the research community. </p>
<p>Some of this was <a href="https://theconversation.com/why-eat-your-vitamins-when-you-can-now-shoot-them-up-16298">absolutely right</a>, yet perhaps the backlash went too far. It overlooked <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273429/pdf/1475-2891-11-7.pdf">some careful science</a> that had hinted, in selected cases, that megadoses of vitamins may treat certain diseases after all.</p>
<p>This is borne out by the new study I mentioned earlier, which <a href="http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30062-4">has shown that</a> taking high doses of vitamin C may help treat lung cancer and <a href="https://www.thebraintumourcharity.org/understanding-brain-tumours/types-of-brain-tumour-adult/glioblastoma/">certain brain tumours</a>. This follows on from <a href="http://stm.sciencemag.org/content/6/222/222ra18.full">previous work</a> proposing to test the use of vitamin C in the treatment of ovarian cancer. </p>
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<a href="https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/166629/original/file-20170425-12629-1jwuts1.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>
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<span class="caption">C for cure?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/stethoscope-red-love-medical-conceptual-text-555960676?src=BkejedQWbZBT1LzIl8KxJQ-1-82">Mawardi Bahar</a></span>
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<p>The new findings come from <a href="http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30062-4">research</a> led by Dr Joshua Schoenfeld of the University of Iowa. The paper was published last month in the journal Cancer Cell, and showed that vitamin C does not fight cancer directly as a drug, but by rendering radiotherapy and certain chemotherapy treatments more effective. </p>
<p>But where Pauling and his followers extolled supplements, Schoenfeld et al are proposing to directly infuse vitamin C into the patient’s bloodstream. It builds on previous findings that <a href="http://annals.org/aim/article/717329/vitamin-c-pharmacokinetics-implications-oral-intravenous-use">showed that</a> tablets taken orally will not deliver enough vitamin C into the body to be effective. </p>
<p>The research has completed a first phase that found the treatment improving survival prospects in mice, and that the vitamin C is safe and tolerable in patients having radio-chemotherapy. But to stress, if there is a successful final outcome to these trials, any treatment would never involve vitamin C pills from the local pharmacy. It would require a well controlled intravenous infusion. </p>
<h2>The way forward</h2>
<p>This research is an example of meticulous science dissecting vitamin fact from fiction. I am optimistic that new discoveries using megadoses will be made in the future. High doses of vitamin C may also be used to treat the pain <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125947/">from postherpetic neuralgia</a>, a nerve-related condition linked to shingles; while preliminary results suggest it may also help treat <a href="http://www.sciencedirect.com/science/article/pii/S0012369216625643">blood poisoning</a> (sepsis). </p>
<p>Megadoses of other water-soluble vitamins have also been proposed, including administering vitamin B3 as a treatment for damaged nerve endings (peripheral neuropathies) after a <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Nicotinamide+riboside%2C+a+form+of+vitamin+B3+and+NAD%2B+precursor%2C+relieves+the+nociceptive+and+aversive+dimensions+of+paclitaxel-induced+peripheral+neuropathy+in+female+rats.">promising study</a> on rats. </p>
<p>There is probably also undiscovered potential among the fat-soluble vitamins – A, D, E and K – but megadoses of them can be dangerous. Too much vitamin A <a href="http://www.healthline.com/health/hypervitaminosis-a">can damage</a> the liver, for instance; while too much vitamin D <a href="http://www.healthline.com/health/hypervitaminosis-d#overview1">can cause</a> everything from fatigue and tinnitus to heart arrhythmias from too much calcium in the blood. </p>
<p>In such cases, the answer might be to design molecules that provide the equivalent of a hyperdose of vitamins but in a very targeted way to reduce the side effects. That is what I have been working on with colleagues at the universities of Aberdeen and Durham, as explained in <a href="https://www.youtube.com/watch?v=8-jiMpNCScM&feature=youtu.be">the clip</a> below. </p>
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<p>We are designing new compounds that activate only one part of the vitamin A response via the retinoic acid receptor, without triggering other receptors. It should be possible to achieve similar results for other vitamins with receptors, most obviously vitamin D. </p>
<p>In conclusion, it certainly looks as though the pendulum swung too far in the other direction in reaction to Pauling. Schoenfeld et al have shown how very precise and careful science can extract the benefits from vitamin supplementation. It’s certainly not a new argument for taking oral supplements, but it is worth watching this space to see what emerges next.</p><img src="https://counter.theconversation.com/content/76472/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter McCaffery receives funding from the BBSRC.</span></em></p>Something exciting is going on – no thanks to the supplements industry.Peter McCaffery, Professor of Biochemistry, University of AberdeenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/735842017-03-06T13:29:53Z2017-03-06T13:29:53ZPancreatic cancer wouldn’t be so deadly if we could just diagnose it earlier<figure><img src="https://images.theconversation.com/files/159352/original/image-20170304-29027-172w8a1.jpg?ixlib=rb-1.1.0&rect=0%2C68%2C511%2C367&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Fluorescence microscopy image of the early stages of pancreatic cancer</span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><p>Pancreatic cancer is extremely difficult to diagnose. The current prognosis for pancreatic cancer is so poor that a UK cancer charity has warned <a href="https://www.pancreaticcancer.org.uk/latest-news/2017/february/pancreatic-cancer-to-become-big-four-killer/">more than 11,000 people</a> are expected to die from the cancer by 2026, and that it will overtake breast cancer to become the <a href="https://www.pancreaticcancer.org.uk/latest-news/2017/february/pancreatic-cancer-to-become-big-four-killer/">fourth-biggest cancer killer</a>.</p>
<p>Even with current treatments, only <a href="http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer">5% of pancreatic cancer patients</a> survive for five years after diagnosis. </p>
<p>The disease has been more in the public conscious recently, following the deaths of <a href="https://theconversation.com/hans-rosling-was-an-incredibly-entertaining-presenter-of-the-facts-and-he-made-a-huge-impact-72751">Swedish statistician Hans Rosling</a> and <a href="https://www.theguardian.com/film/2017/jan/28/john-hurt-obituary">British actors John Hurt</a> and <a href="https://www.theguardian.com/film/2016/jan/14/alan-rickman-obituary">Alan Rickman</a>. And though many have quoted the line alongside these reports that survival rates have <a href="http://www.futuremedicine.com/doi/full/10.2217/fon-2016-0010">not improved since the 1960s</a>, for many years scientists have been working on the crucial early diagnosis methods that could save future patients.</p>
<h2>Symptoms</h2>
<p>Some of the best diagnosed forms of cancer are easily identified with symptoms that everyone is aware of. Melanoma (skin cancer), for example, can be spotted when moles change colour, size and/or shape; <a href="https://www.theguardian.com/society/2014/sep/22/cancer-late-diagnosis-half-patients">93% of cases</a> are diagnosed in stage one or two because patients can catch it early on themselves. The majority of breast cancer, 83%, is also caught in these early stages as most people have been made aware of the symptoms and know how to check for them.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/159548/original/image-20170306-20753-yxnyfh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/159548/original/image-20170306-20753-yxnyfh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=464&fit=crop&dpr=1 600w, https://images.theconversation.com/files/159548/original/image-20170306-20753-yxnyfh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=464&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/159548/original/image-20170306-20753-yxnyfh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=464&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/159548/original/image-20170306-20753-yxnyfh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=583&fit=crop&dpr=1 754w, https://images.theconversation.com/files/159548/original/image-20170306-20753-yxnyfh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=583&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/159548/original/image-20170306-20753-yxnyfh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=583&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The pancreas organ secretes hormones such as insulin, and produces digestive juices.</span>
<span class="attribution"><span class="source">www.shutterstock.com</span></span>
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</figure>
<p>Unlike breast, skin or one of a number of other easily recognisable cancers, public knowledge of pancreatic cancer symptoms is very low: a <a href="https://www.pancreaticcancer.org.uk/media/491284/comres-awareness-survey-report-2015.pdf">recent survey</a> found that more than 70% of people were unable to name a single symptom of the disease unprompted. </p>
<p>However, even if a patient is aware of <a href="http://www.nhs.uk/Conditions/Cancer-of-the-pancreas/Pages/Introduction.aspx#symptoms">the symptoms</a> – which include jaundice, abdominal pain, weight loss, changes to appetite and indigestion – they could all easily be attributed to other causes, such as pancreatitis or an ulcer. </p>
<p>On top of this, pancreatic cancer symptoms don’t appear until late on in the disease. It is for these reasons that <a href="http://www.nature.com/nrclinonc/journal/v10/n6/full/nrclinonc.2013.66.html">80% of pancreatic cancer patients</a> don’t find out they have the disease until it has reached an advanced stage and spread around the body. Once the cancer has begun to spread around the body it makes surgical intervention – the best current treatment – impossible. </p>
<h2>Hidden cancer</h2>
<p>Detecting pancreatic tumours is not an easy thing to to do, even when symptoms are present. The pancreas is hidden deep in the body, behind the stomach, making it hard for a doctor to feel for tumours during an examination. Its location also creates problems with imaging and taking biopsies when a patient has been referred onwards. Even specialised CT and MRI scans can miss small lesions that indicate the presence of pancreatic cancer.</p>
<p>Blood tests can also be carried out to measure levels of the biomarker – molecules used to identify the disease – carbohydrate antigen 19-9 (CA19-9). The problem with CA19-9 is that not all pancreatic cancers produce the marker and other diseases can also lead to high levels of the protein.</p>
<h2>Quick diagnosis?</h2>
<p>We now know that pancreatic cancer <a href="http://www.nature.com/nature/journal/v467/n7319/abs/nature09515.html">takes years</a> to develop into a tumour detectable by current methods. So, potentially, there is a window for diagnoses long before a tumour develops and, with the rise in cases predicted, the need to use this time is urgent. </p>
<p>At present there is no established early detection technique, but moves are being made to improve the diagnosis of pancreatic cancer patients and hopefully catch the illness before it gets too late. Recently a <a href="http://www.nature.com/articles/s41551-016-0021">new biomarker</a> was identified that detects <a href="https://www.newscientist.com/article/2120411-blood-test-could-catch-pancreatic-cancer-before-its-too-late/">pancreatic tumours in blood samples</a>. Following a positive study, this detection technique could be the cheap and sensitive tool for diagnosing the earliest stages of the disease that researchers have been striving for.</p>
<p>The research investigated the use of <a href="https://www.sciencemag.org/custom-publishing/technology-features/membrane-messengers-extracellular-vesicles">extracellular vesicles</a> to detect pancreatic cancer. Extracellular vesicles are tiny membrane-bound packages released by cells. They are secreted into the circulatory system and can be easily found in the blood. Though they were previously dismissed as debris, it is now known that these vesicles carry biomarkers from the cells that produce them.</p>
<p>Using this new detection method the researchers were able to identify early-stage pancreatic cancer in more than 90% of the 59 patients who took part in the pilot study. The technique was even able to distinguish between between cancer and pancreatitis. This proof-of-concept study shows the potential of a non-invasive blood test to detect pancreatic cancer. But more work is required to further validate these findings and to fully automate the test so it can be carried out on a larger scale. </p>
<p>If this test is shown to be accurate in larger trials it could lead to non-invasive large-scale screening for pancreatic cancer. Screening <a href="http://www.nhs.uk/Livewell/preventing-cancer/Pages/cancer-screening.aspx">for other types of cancer</a> – such as cervical cancer with smear tests, mammograms for breast cancer, and tests for bowel cancer has revolutionised patient outcome, and this test could very well have the same impact for pancreatic cancer patients.</p>
<p>Though there isn’t an easy way to give a definitive result for pancreatic cancer diagnosis just yet, the work is being done to get there – and tests such as this could potentially save the lives of thousands worldwide.</p><img src="https://counter.theconversation.com/content/73584/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>William Hill receives funding from the MRC. The lab has received funding from Amser Justin Time and Pancreatic Cancer UK.</span></em></p>Pancreatic cancer has long been known as the “silent killer” but why is it so difficult to detect?William Hill, PhD Student Studying Pancreatic Cancer, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/726992017-02-09T14:36:41Z2017-02-09T14:36:41ZThis new treatment could make pancreatic cancer a manageable disease<figure><img src="https://images.theconversation.com/files/156177/original/image-20170209-8651-1u7xx9n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pancreatic cancer has an extremely low five-year survival rate.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-examine-xray-picture-pancreas-394501441?src=ZAipz-ILgUhE5qEydPNyAg-1-0">Shutterstock</a></span></figcaption></figure><p>Cancer is among the leading causes of death worldwide. There were approximately 14m new cases diagnosed and <a href="http://www.cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer">8.2m cancer related deaths in 2012</a>. This figure is expected to rise by about 70% over the next two decades. </p>
<p>Pancreatic cancer is the eighth most common cause of cancer-related mortality worldwide, with <a href="https://www.pancreaticcancer.org.uk/types">incidence almost equalling mortality</a> – that is, almost as many die from the disease each year as develop it. There are <a href="http://www.nature.com/nrc/journal/v15/n10/full/nrc4025.html">several types of pancreatic cancer</a>, but more than 90% of cases are <a href="https://www.pancreaticcancer.org.uk/types">pancreatic ductal adenocarcinomas (PDAC)</a>. PDAC has one of the lowest five-year survival rates as well as a general resistance to chemotherapeutic approaches. As a result, the treatment of PDAC remains a major challenge in oncology.</p>
<p>There is a common theme in some of the most prolific aggressive cancers, and that is a protein known as <a href="https://www.ncbi.nlm.nih.gov/pubmed/27186425">S100P</a>. This protein is highly expressed in pancreatic cancer and once this protein is activated it results in signalling changes that tell the cell to grow and divide remarkably quickly. This induces the cells to spread and create new cancerous growths around the body. This makes <a href="https://www.ncbi.nlm.nih.gov/pubmed/15305381">S100P a great target</a> for developing new drugs to prevent the spread of aggressive cancers – and pancreatic cancer in particular.</p>
<h2>Seeking a fix</h2>
<p>Scientists at the University of Hertfordshire, in collaboration with Dr Tatjana Crnogorac-Jurcevic of Barts Cancer Institute, Queen Mary University of London, used computational chemistry methods to design new compounds that would in theory prevent S100P from being activated. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/156176/original/image-20170209-8637-1kz0eaz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/156176/original/image-20170209-8637-1kz0eaz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/156176/original/image-20170209-8637-1kz0eaz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/156176/original/image-20170209-8637-1kz0eaz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/156176/original/image-20170209-8637-1kz0eaz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/156176/original/image-20170209-8637-1kz0eaz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/156176/original/image-20170209-8637-1kz0eaz.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">Photomicrograph of CT (CAT) scan-guided fine needle aspirate (FNA) cytology of a pancreatic mass showing malignant cells indicating adenocarcinoma.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/success">Shutterstock</a></span>
</figcaption>
</figure>
<p>In a project funded by the charity Worldwide Cancer Research, Dr Stewart Kirton of the University of Hertfordshire designed the structures of new drugs based on Cromolyn, a drug that can be used to prevent allergy-induced asthma. These new compounds were then synthesised by Hertfordshire’s Dr Sharon Rossiter and her team of chemists. I started my PhD with the aim to identify the lead compounds that could be further developed as a suitable drug that would present the further spreading of the cancer. My supervisory team included scientists with a wide variety of disciplines: Dr Louise Mackenzie (pharmacologist), Dr Sharon Rossiter (chemist), Dr David Chau (cell biologist) and Dr Pryank Patel (biochemist), whose expertise had helped to focus my research.</p>
<p>I then <a href="https://bps.conference-services.net/resources/344/3974/pdf/PHARM15_0326.pdf">used molecular biology techniques</a> to screen a bank of 93 synthetic compounds for their ability to prevent the activation of S100P. From that work, 18 potential drugs were identified and then tested to see how toxic they are to cells. </p>
<p>The compounds themselves did not kill the cancer cells, but they did prevent them from migrating. This is an excellent profile for a drug to treat this type of cancer, since in theory any drug that worked in this way would both slow down the progression of the cancer and make it more vulnerable to chemotherapy. </p>
<p>The next stages are to look at ways to make sure that there are as few side effects possible by making small changes to the structure of the most promising candidate drugs. If successful, it might make a difference for patients between no survival – and a prolonged life. One day, pancreatic cancer may even become a manageable disease.</p><img src="https://counter.theconversation.com/content/72699/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The research project at the University of Hertfordshire as a whole was originally funded by the charity Worldwide Cancer Research. The supervisory team for Deborrah Ogbeni’s PhD is: Dr Louise Mackenzie, Dr Sharon Rossiter, Dr David Chau and Dr Pryank Patel. The PhD is part of a much bigger project that originates from Dr Sharon Rossiter and Dr Stewart Kirton’s work on S100P at the University of Hertfordshire, plus a collaborator at the Barts Cancer Institute, Queen Mary University of London; Dr Tatjana Crnogorac-Jurcevic.</span></em></p><p class="fine-print"><em><span>Louise Mackenzie 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>It’s early days, but hope is on the horizon when it comes to one of the deadliest cancers.Deborah Ogbeni, PhD candidate, University of HertfordshireLouise Mackenzie, Senior Lecturer Pharmacology, University of HertfordshireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/624962016-07-17T20:08:54Z2016-07-17T20:08:54ZGPs unlikely to pick up certain cancers right away because it’s not the most likely diagnosis<figure><img src="https://images.theconversation.com/files/130622/original/image-20160714-2115-zirebx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CT scans are expensive and carry their own risks, so a GP won't send you for one without good reason. </span> <span class="attribution"><span class="source">www.shutterstock.com</span></span></figcaption></figure><p>Diagnosing cancer early is important for improving the chances of long-term survival from the disease. Perceived delays in cancer diagnosis are a common cause of distress for patients and their families – and a frequent source of legal complaints. </p>
<p>Most patients with cancer first present with symptoms to their GP, and so the GP plays a critical role in early cancer diagnosis. But this is a challenging task, and as our new paper in the <a href="https://www.mja.com.au/journal/2016/205/2/presentations-general-practice-cancer-diagnosis-victoria-cross-sectional-survey">Medical Journal of Australia</a> shows, it is even more challenging for certain cancers.</p>
<p>As part of a patient experience survey of more than 1,500 patients attending a Victorian cancer hospital, we examined patients’ visits to their GP and time taken to see a cancer specialist preceding their cancer diagnosis. </p>
<p>We showed that people with myeloma (cancer of the plasma cells in bone marrow), pancreatic or brain cancers were more likely to have had multiple visits to their GP before referral for suspected cancer. In contrast, women with breast cancer were often referred after the first GP visit and were most likely to be diagnosed within three months of the onset of their symptoms.</p>
<p>There are some important reasons why diagnosing pancreatic, brain tumours and myeloma are the most challenging for GPs.</p>
<h2>Symptoms more likely something else</h2>
<p>These are all relatively rare cancers and so a GP might only see a patient with each of these cancers once every three to five years. More importantly, the symptoms with which these cancers first present are usually caused by a much more common, benign condition. </p>
<p>For example, pancreatic cancer may initially cause abdominal or back pain, indigestion, or reduced appetite. Only later may people develop jaundice, which is a much more serious and specific symptom of pancreatic cancer, but one that’s usually associated with later-stage disease. </p>
<p>Brain cancers usually first present with a headache and only rarely with more specific symptoms such as muscle weakness or a seizure. Myeloma also has non-specific symptoms such as fatigue, back pain and more frequent infections.</p>
<p>The first time someone visits their GP with indigestion, for example, the doctor is unlikely to consider pancreatic cancer as a likely cause for their symptoms because it is so unlikely (<a href="http://www.nature.com/bjc/journal/v106/n12/full/bjc2012190a.html">less than a one in 100 chance</a>). Even if that patient had also lost weight, the likelihood it is due to pancreatic cancer is <a href="http://www.nature.com/bjc/journal/v106/n12/full/bjc2012190a.html">still only about one in 25</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/130623/original/image-20160714-2147-vff7j2.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">If you go to see your doctor because you have indigestion, they won’t jump to a diagnosis of pancreatic cancer.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
</figcaption>
</figure>
<p>To add to the complexity, a GP may be more likely to consider stomach rather than pancreatic cancer because it is a more common cancer causing this symptom. A GP may therefore refer this patient for an endoscopy to check for stomach cancer instead of a CT scan, the preferred initial test needed to diagnose pancreatic cancer, thereby delaying diagnosis.</p>
<p>A GP has to be able to assess the likelihood of multiple possible causes of symptoms, creating their own internal ranking of possible diagnoses. Cancer will often be quite low down this list of possible causes simply because, statistically, it is less likely. Only when a patient develops additional symptoms and visits their GP a second or third time will cancer be bumped up this list and specific tests ordered, usually to rule out cancer as a possible diagnosis.</p>
<p>Our study found more than a third of patients with bowel cancer took more than three months from recognising there was something wrong to first seeing a hospital specialist. This reflects a significant problem of long waiting times for colonoscopy in the public system. We know from <a href="http://www.crisp.org.au/">related research</a> at the University of Melbourne that, in Australia, we are overusing colonoscopy and we need to target the use of this test better to those most likely to benefit.</p>
<h2>How soon is too soon?</h2>
<p>So how soon should a doctor order key cancer diagnostic tests such as CT scans or refer the patient for an endoscopy? </p>
<p>A <a href="http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70588-6/abstract">large study of patients in the UK</a> showed people want to be investigated promptly if their chance of having cancer was as little as one in 100. </p>
<p>But many tests to diagnose cancer are quite invasive, such as colonoscopy, and can have significant risks, such as puncturing your bowel. There is also <a href="http://www.scientificamerican.com/article/how-much-ct-scans-increase-risk-cancer/">growing recognition of the harms</a> of radiation from multiple CT scans, including causing cancers. </p>
<p>In a publicly funded health-care system, we must also be cognisant of the economic costs of ordering moderately expensive tests when the chance of finding an abnormality is low. This is a very sensitive issue in the context of arguments about the growing Medicare budget, but we need an open debate about how to deliver more rational and cost-effective use of limited and potentially harmful diagnostic tests while still diagnosing cancer early.</p><img src="https://counter.theconversation.com/content/62496/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jon Emery receives funding from the National Health and Medical Research Council, Cancer Australia, Cancer Council Victoria, Victorian Cancer Agency and Cancer Research UK.. </span></em></p>A new research paper has found some cancers aren’t picked up by GPs in the first or second appointments, but it’s because cancer is usually an unlikely explanation for a patient’s symptoms.Jon Emery, Professor of Primary Care Cancer Research, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/580632016-06-06T20:06:44Z2016-06-06T20:06:44ZHow Australians Die: cause #2 – cancers<figure><img src="https://images.theconversation.com/files/122434/original/image-20160513-27184-134upnp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Age-standardised cancer death rates have been falling in Australia.</span> <span class="attribution"><span class="source">from shutterstock.com</span></span></figcaption></figure><p><em>This is the second in the <a href="https://theconversation.com/au/topics/how-australians-die">How Australians Die</a> series that focuses on the country’s top five causes of death and how we can drive down rates of these illnesses. Tomorrow’s piece will explore the third leading cause of death: Alzheimer’s. You can also read our first article on <a href="https://theconversation.com/how-australians-die-cause-1-heart-diseases-and-stroke-57423">heart diseases and stroke</a>.</em></p>
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<p>Described as <a href="http://www.amazon.com/The-Emperor-All-Maladies-Biography/dp/1439170916">“The Emperor of All Maladies”</a> by Pulitzer Prize-winning author and researcher <a href="http://authors.simonandschuster.com/Siddhartha-Mukherjee/49784674">Siddartha Mukherjee</a>, cancer is often seen as a modern disease. But scientists have found evidence of it in <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003131/">dinosaur fossils</a> and human cases appear in literature spanning four millennia. </p>
<p>The Egyptian physician Imhotep <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997531/">vividly described advanced breast cancer</a> in 2600 BC as “<a href="https://books.google.com.au/books?id=hgx0sJvphNkC&pg=PA40&lpg=PA40&dq=cool+hard+dense+as+hemat+fruit&source=bl&ots=1FQSiRjT-C&sig=ZgjwyopC7l-WgIh-xJF1s6IVGfM&hl=en&sa=X&ved=0ahUKEwjZ_emD3pLNAhVJo5QKHV1JBYkQ6AEIHDAA#v=onepage&q=cool%20hard%20dense%20as%20hemat%20fruit&f=false">a bulging mass in the breast</a>”: cool, hard and spreading beneath the skin. Under the section “Therapy”, Imhotep solemnly recorded: “<a href="https://books.google.com.au/books?id=hgx0sJvphNkC&pg=PA40&lpg=PA40&dq=cool+hard+dense+as+hemat+fruit&source=bl&ots=1FQSiRjT-C&sig=ZgjwyopC7l-WgIh-xJF1s6IVGfM&hl=en&sa=X&ved=0ahUKEwjZ_emD3pLNAhVJo5QKHV1JBYkQ6AEIHDAA#v=onepage&q=%22there%20is%20none%22&f=false">There is none.</a>”</p>
<p>An early modern <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2128854/pdf/medcht00065-0003.pdf">publication on cancer comes from 1818</a>. Written by physician George Wagstaff, it includes a number of gruesome case studies such as that of “fungus haematodes”, or blood fungus in the lungs. </p>
<p>Since then, more than three million scientific papers have been published on the subject, 159,000 of them in 2015 alone.</p>
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<p>Between 1968 and 2013 <a href="http://www.aihw.gov.au/acim-books/">cancer deaths in Australia</a> increased from 17,032 to 44,308, a rise of 160%. However, taking into account the increase in population (94%) and the increase in average age (34%) over the same period, there has been a decline in the age-standardised cancer death rate overall in Australia. The chance of a cancer death before the age of 75 in 1968 was 12.8%. This has fallen to 9.4% in 2013.</p>
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<p>Cancer is made up of around 200 distinct illnesses united by the uncontrolled growth of human cells. The diversity of mechanisms by which different cancer types both grow and evade treatment means that many separate breakthroughs will be required to combat all cancers.</p>
<p>Currently, seven cancer types are listed in the <a href="http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/by%20Subject/3303.0%7E2014%7EMain%20Features%7ELeading%20Causes%20of%20Death%7E10001">top 20 causes of death</a> in Australia. These are cancers of the lung, blood and lymph, bowel, prostate, breast, pancreas and skin.</p>
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<figure><figcaption>The How Australians Die series has combined all cancer deaths to make them the second leading cause of death after heart diseases and stroke. Alzheimer’s is number 3, respiratory diseases, number 4 and diabetes, number 5.</figcaption></figure>
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<h2>Lung cancer</h2>
<p>This is the number one cancer killer, ranking number four in overall causes of death. <a href="http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129555176">Most (80%) lung cancers are still attributable to tobacco smoking</a>, either directly or through passive smoking. Australia is leading the world in reducing smoking rates and fewer than 13% of <a href="http://www.tobaccoinaustralia.org.au/chapter-1-prevalence/1-3-prevalence-of-smoking-adults">Australian adults now smoke</a>, with fewer lung cancer cases as a result.</p>
<p>Sadly, lung cancer survival remains poor due in part to late detection. Less than 15% of people are still alive five years after diagnosis although new <a href="http://bmcpulmmed.biomedcentral.com/articles/10.1186/1471-2466-12-77">immunotherapy treatments</a> that help the immune system destroy cancer cells are prolonging survival for some patients. </p>
<p>Also, <a href="http://www.ncbi.nlm.nih.gov/pubmed/26763803">trials screening people at high risk</a>, particularly smokers, using chest CT scans are showing promise in catching the disease earlier and at a more curable stage.</p>
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<img alt="" src="https://images.theconversation.com/files/122435/original/image-20160513-27184-hjnzfw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/122435/original/image-20160513-27184-hjnzfw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122435/original/image-20160513-27184-hjnzfw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122435/original/image-20160513-27184-hjnzfw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122435/original/image-20160513-27184-hjnzfw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122435/original/image-20160513-27184-hjnzfw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122435/original/image-20160513-27184-hjnzfw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Most lung cancers are attributable to tobacco smoke.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/kylesatori/4650255057/in/photolist-85VLPk-6zcf1r-pCJrZ7-8P8iX-7jzoZ8-55ZgRD-bmiUwX-caLjtm-bV7KzN-8ZDpWJ-6hzGDX-nzVzhZ-6hzGKD-nu9cJ-5THWVF-csEp2u-pcbutn-cx35sj-GGW4-RmCwd-ouvRb4-6txjrq-nk8yxk-cQjrzu-6LkHp3-fhGr8v-qYBCkY-9E8Ros-DcrJk-cepTSU-cPCph5-9P6oma-a7q6zT-Btw3To-9sRHm4-64L1oM-8JBeip-7Xutv2-dpHHp4-ptDVJf-jtjAc-aaR9Af-jtjAb-6TPX8J-7jz8aF-5FDUvv-dm6vt-67K1Ww-a8Bf8a-9vhUju">Bruno de Souza Leão/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Blood and lymph cancer (including leukaemia)</h2>
<p>Cancers of the lymph glands (lymphomas) affect the body’s infection fighting mechanism and come in two types: Hodgkin and Non Hodgkin lymphoma. Blood cancers are called leukaemia and classified as either acute (fast growing) or chronic (slow growing). </p>
<p>Combined, these cancers are referred to as haematological cancers and they caused 4,275 deaths in Australia in 2013 (made up mostly of lymphoma and leukaemia caused deaths). For each, there are <a href="http://www.nhs.uk/ipgmedia/national/Lymphoma%20Association/Assets/Leukaemiaandlymphoma-thedifference.pdf">sub types with different features</a>, treatments and survival rates. Little is known about the causes of these cancers but survival is improving for many types.</p>
<h2>Large bowel cancer</h2>
<p>In 2014, 4,169 people died of bowel cancer (0.9% chance of death before age 75) compared to 2,500 in 1968 (1.9%). These cancers can often be treated successfully if found early through faecal blood testing such as in the <a href="http://www.cancerscreening.gov.au/bowel">National Bowel Cancer Screening Program</a>. </p>
<p>However, since the program began in 2006, <a href="http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/nbcsp-fact-sheet">only 40% of those invited have done the test</a>. Despite men being diagnosed more, at a later stage and being more likely to die from bowel cancer, they are less likely than women to participate.</p>
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<h2>Prostate cancer</h2>
<p>In 2014, 3,102 Australian men died of prostate cancer, up from 963 in 1968. Diagnosis and death are rare for those under 50 but the disease becomes increasingly common in older men with over half of prostate cancer deaths occurring after 80. Causes are unknown making preventative options hard to identify.</p>
<p>Although diagnosis is common, only one in six men who are diagnosed die of prostate cancer. The five year <a href="http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129545133">survival rates exceed 90%</a>, giving prostate cancer the reputation of being a disease one dies with rather than from. However the large number of cases, particularly in much older men, mean it remains a major cancer killer.</p>
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<img alt="" src="https://images.theconversation.com/files/125248/original/image-20160605-11620-1340d2z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/125248/original/image-20160605-11620-1340d2z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=719&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125248/original/image-20160605-11620-1340d2z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=719&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125248/original/image-20160605-11620-1340d2z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=719&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125248/original/image-20160605-11620-1340d2z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=904&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125248/original/image-20160605-11620-1340d2z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=904&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125248/original/image-20160605-11620-1340d2z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=904&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">More breast cancers are not being detected at a curable stage.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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<p>Surgery and <a href="http://www.cancer.org.au/about-cancer/after-a-diagnosis/after-a-diagnosis-of-prostate-cancer.html">radiotherapy are the most common</a> treatments. Hormone therapy, recently combined at the beginning with chemotherapy, can often control more widespread disease for long periods. </p>
<h2>Breast cancer</h2>
<p>Perhaps the highest-profile cancer, progress in breast cancer has been strong. However, 2,844 Australians, including about 30 men, still died of breast cancer in 2014 in Australia. </p>
<p>Breast cancer is now divided into <a href="https://www.bcna.org.au/understanding-breast-cancer/types-of-breast-cancer/">different sub-types</a>, each with its own behaviour. Understanding this has allowed more personalised therapy for many patients, which has improved treatment outcomes.</p>
<p>Mammographic screening has <a href="http://www.abc.net.au/health/features/stories/2014/03/14/3962769.htm">attracted some controversy</a> because of possible over-diagnosis. But with participation rates well above 50%, and more cancers being detected at more curable stages, it has likely contributed to the rise of five year survivals to 90%.</p>
<h2>Pancreatic cancer</h2>
<p>Little progress has been made in pancreatic cancer that took 2,547 Australians in 2014, compared to <a href="http://www.aihw.gov.au/acim-books/">797 in 1968</a>. Smoking, obesity and some pesticides can contribute to pancreatic cancer risk. </p>
<p>An absence of signs and tests make early detection uncommon and little progress has been made in identifying important drivers of pancreatic cancer growth. As diagnosis often occurs at an advanced stage and focused treatments are lacking, outcomes are poor with a <a href="http://www.cancer.org.au/about-cancer/types-of-cancer/pancreatic-cancer.html">five year survival rate of only 5%</a>.</p>
<h2>Skin cancers</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/125249/original/image-20160605-11620-re3k4r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/125249/original/image-20160605-11620-re3k4r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=722&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125249/original/image-20160605-11620-re3k4r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=722&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125249/original/image-20160605-11620-re3k4r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=722&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125249/original/image-20160605-11620-re3k4r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=908&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125249/original/image-20160605-11620-re3k4r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=908&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125249/original/image-20160605-11620-re3k4r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=908&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">Melanoma is the leading cause of skin cancer deaths.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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</figure>
<p>Of the 2,067 skin cancer deaths, approximately 1,600 were due to melanoma while non-melanoma skin cancer (NMSC), a far more common but less lethal form, claimed the others in 2014. Excessive ultraviolet radiation from sunlight remains the main cause for both.</p>
<p>Recently, New Zealand surpassed Australia <a href="http://www.jidonline.org/article/S0022-202X%2816%2900488-7/pdf">as the number one skin cancer nation</a> in the world. Melanoma cases are falling in Australia, probably due to prevention efforts.</p>
<p>Generally, treatment of early stage disease is highly successful with a greater than 95% five year survival rate. Even for advanced melanoma, <a href="http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/melanoma">new immunotherapy treatments are increasing survival times</a>.</p><img src="https://counter.theconversation.com/content/58063/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Terry Slevin works for Cancer Council WA and serves as a spokesperson for Cancer Council Australia. He has been an investigator on various cancer research projects funded by state and national research funding organisations.
</span></em></p><p class="fine-print"><em><span>Andrew Redfern receives funding from the Cancer Council WA and the Health Department of WA.</span></em></p>Currently, seven cancer types are listed in the top 20 causes of death in Australia. These are cancers of the lung, blood and lymph, bowel, prostate, breast, pancreas, skin and some childhood cancers.Terry Slevin, Adjunct Professor, School of Psychology and Speech Pathology, Curtin University; Education and Research Director, Cancer Council WA; Chair, Occupational and Environmental Cancer Committee, Cancer Council AustraliaAndrew Redfern, Senior Lecturer, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/352922015-01-20T06:18:35Z2015-01-20T06:18:35ZHow deadly cancer may actually be spread by survival mechanism<figure><img src="https://images.theconversation.com/files/68845/original/image-20150113-28455-zxfu0l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The actions of cells underpin new thinking about pancreatic cancer, which took the life of Apple's Steve Jobs. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/jamesmitchell/2565317822/sizes/o/in/photolist-4UFVBC-PQryd-PR3Bk-atUU1b-atmFQG-njDWVF-N9vns-b2Cbsk-b2Cbgt-b2CbdH-fCyLS1-atTMKv-aX3Nvk-atgskP-atnkuR-atqeSe-atJjxP-7ouSZj-atEwVT-atHcSG-atjecF-atm5vZ-7N9gtP-c4TiBy-atjpuM-83QwWp-fmspcP-9uQfFD-atsvzj-att4Rf-5fnMQj-83TDFL-85tiYG-atLZvu-atJj8x-atgMz6-baSZsK-x9aCj-fEKA4t-aAKFAs-avHR5C-7M6Jvx-aPZCei-aPZCFt-cSzo3W-ec3ZF-oX54Xh-av9vEA-atXjhg-c3NbHb-avRq5s/">James Mitchell</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Pancreatic cancer is a devastating disease. With a <a href="http://www.cancerresearchuk.org/cancer-info/cancerstats">ten-year survival rate of just 1%</a>, it has the poorest prognosis of all solid tumours. The main reason for this is that tumours of the pancreas largely develop without symptoms. Therefore, by the time many patients are diagnosed, the disease has advanced to a metastatic and incurable stage.</p>
<p>Metastasis, which describes when cancer cells leave (or disseminate from) the primary tumour and spread (or invade) to other organs in the body to form secondary tumours, is the main cause of cancer-related death. Hope for improved prognoses for many cancer patients lie in the ability to detect and diagnose the disease before it reaches this deadly stage.</p>
<p>Currently, there are no programmes available anywhere in the world <a href="http://www.pancreaticcancer.org.uk">to screen for pancreatic cancer</a> in the general population. The main reason for this is that we lack the suitable screening and diagnostic tools to detect at-risk individuals. In order to develop new methods to detect and diagnose this disease earlier, we need basic research to increase our knowledge and understanding of how this disease starts.</p>
<p>In recent years our knowledge of the genetics and pathology of pancreatic cancer has improved considerably. Genetic profiling of human disease has allowed researchers to estimate the timing of the development of the various stages of the disease and revealed that, on average, a primary tumour expands and <a href="http://www.nature.com/nature/journal/v467/n7319/abs/nature09515.html">grows within the pancreas for a decade</a> before spreading to other organs.</p>
<p>This suggests that there is a broad window of opportunity to detect and diagnose the cancer early – providing we have the right tools. However, we still do not know enough about how this disease begins and develops at a cellular level.</p>
<h2>A clear progression</h2>
<p>Under normal, healthy conditions cells <a href="https://theconversation.com/how-self-destructing-cells-may-hold-key-to-cancer-cure-31707">undergo a programme of cell death</a>, which causes them to self-destruct when their use is over. Over a cell’s life span, mutations can occur in specific genes, which transform the cell to become abnormal. Transformation of a cell disrupts this vital process of self-destruction and the cell continues to grow and divide without control. Therefore, transformation of cells is the first step in cancer development.</p>
<p>Pancreatic ductal adenocarcinoma, or PDAC, is the most common form of pancreatic cancer, which begins with non-invasive precursor lesions. These microscopic lesions develop primarily from the epithelial cells that line the ducts in the exocrine pancreas that become transformed when a specific cancer-causing gene (or oncogene) called KRas becomes mutated. KRas mutations are detected <a>in around 90% of all human PDACs</a>) and are known as the founder mutation in PDAC.</p>
<h2>Genetic profiling</h2>
<p>It is generally considered that PDAC develops from grade I precursor lesions to grade III and then to metastatic disease. Researchers have generated genetic “maps” of a sample of human tumours, <a href="http://www.nature.com/nature/journal/v467/n7319/abs/nature09515.html">and found</a> that PDAC genetically evolves over time. Metastatic or secondary stage tumours are genetically similar to the initial pre-invasive tumour. This suggests that founder mutations such the KRas mutation, are required for all stages of the disease’s progression. However, cells within a primary tumour must acquire additional genetic mutations to become metastatic or invasive.</p>
<p>However, <a href="http://www.ncbi.nlm.nih.gov/pubmed/22265420">a more recent study</a> suggests that our understanding of how this disease starts requires a new perspective. Using cutting-edge genetic and imaging tools, researchers have tracked transformed pancreatic epithelial cells in real time. This revealed that transformed cells (expressing KRas mutations) were detected in the bloodstream and had spread to the liver before a primary tumour was detected in the pancreas. In fact, KRas-transformed cells escaped from early grade precursor lesions.</p>
<p>It is possible that although these mutant cells spread out of the pancreas at very early stages of the disease, once seeded in secondary sites they become dormant or grow at a slower rate and are not detected until years later. What remains unclear is the process by which KRas-transformed cells leave the pancreas to enter the bloodstream and metastasise to other organs.</p>
<h2>Out of the frying pan, into the fire</h2>
<p>At the <a href="http://www.cardiff.ac.uk/research/cancer-stem-cell">European Cancer Stem Cell Research Institute</a>(ECSCRI) at Cardiff University, the primary focus of our research is to gain a better understanding of early pancreatic cancer. In particular, how precursor lesions start and develop once a normal cell becomes transformed. To further our research into pancreatic cancer, we study epithelial cell biology; how epithelial cells interact and communicate with each other within a tissue.</p>
<p>Along with muscle, nervous and connective tissue, epithelium – made up of epithelial cells – is one of the four major tissue types in the human body. The main function of an epithelium is to act as a tight barrier that protects our organs from potential harm in the external environment. Under normal conditions, epithelial cells tightly bind to each other to form this protective barrier. In addition to providing a physical structure to the tissue, each epithelial cell receives and communicates multiple networks of signals through cell-to-cell connections and these give cells instructions on position within a tissue as well as function.</p>
<p>So what happens to this communication network when epithelial cells become transformed but remain in direct contact with their normal neighbours? Working as a postdoctoral researcher in Yasu Fujita’s lab, then at UCL, London, I showed that <a href="http://www.ncbi.nlm.nih.gov/pubmed/19287376">normal cells detect and eliminate Ras-transformed cells</a>, which may act as an anti-cancer strategy. On the other hand, the signal to remove a mutant cell may act as a trigger to escape and therefore may promote the early spread of the mutant cells to other tissues.</p>
<p>At ECSCRI, and with the support of our collaborator, Owen Sansom and his team at the Beatson Institute in Glasgow, we are exploring both of these scenarios in pancreatic cancer. A big question is how normal cells detect the mutant cells – and we are currently investigating a specific cell-to-cell communication signal that could trigger this process.</p>
<p>One of the major risk factors for PDAC is pancreatitis, an inflammatory disease of the pancreas usually caused by alcohol misuse, which can significantly damage the tissue. With Ole Petersen’s team at Cardiff University – experts in pancreatitis – we are exploring whether and how pancreatitis alters cell-to-cell communication between normal and KRas-transformed cells.</p>
<p>We hope that our research will add knowledge to our understanding of how pancreatic cancer starts and develops from the earliest stages. An increased understanding will bring about the development of new screening, detection and diagnostic tools sooner, and may help increase the number of people living longer with this deadly disease.</p><img src="https://counter.theconversation.com/content/35292/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Catherine Hogan receives funding from European Cancer Stem Cell Research Institute, Pancreatic Cancer UK, CRUK Development Fund, Royal Society Research grant, Medical Research Council, Amser Justin Time</span></em></p>Pancreatic cancer is a devastating disease. With a ten-year survival rate of just 1%, it has the poorest prognosis of all solid tumours. The main reason for this is that tumours of the pancreas largely…Catherine Hogan, Research Fellow, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/316582014-09-15T10:00:14Z2014-09-15T10:00:14ZLessons from the war on terror could help the war on cancer<figure><img src="https://images.theconversation.com/files/58917/original/fxjynrnd-1410533124.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We can't let terrorists win.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/ahikilledhim/1807971049">ahikilledhim</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>There may seem to be no connection between terrorism and cancer. But that is an oversight. If considered closely, it is easy to see that both exhibit loss of control present in “normal” conditions and are often detected only when they have already invaded and spread to different sites.</p>
<p>So could insights gained from studying communication networks in terrorism help the oncologist decide which therapy is better for which cancer patient? Mary McGuire of University of Texas Medical School thinks so. In a new study, published in <a href="http://dx.doi.org/10.1287/deca.2014.0301">Decision Analysis</a>, she finds similarities between communication networks of successful terrorist organisations and those of molecular communications in cancers. These similarities could be exploited to build better treatment regimes.</p>
<h2>Making networks resilient</h2>
<p>McGuire’s work began when she came across the case of a multi-year survivor of pancreatic cancer, a disease that typically kills in less than six months of detection. She used the patient’s data to generate the most likely biological “pathways”, or signalling networks, that cells use to sense their environment and communicate with each other. </p>
<p>What she found was a “star-shaped” network – that is, a network in which the central “leader” or “hub” connects with every other entity, ensuring fast and flexible communication. Such star-shaped networks are also adopted by <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0013448">successful terrorist movements</a> because they are resilient to cascading failures – such as blackouts caused by power-grid failure – which can occur when other parts of the network communicate with each other directly through multiple connections.</p>
<p>However, these star-shaped networks are not something that cancer comes up with by itself. Such networks are used by normal cells of our body to communicate with each other. But networks, which the cancer cells of McGuire’s patient used, replaced the entities or molecules found in a non-cancer star network with those that helped the cancer to survive. In other words, this cancer took over the most efficient biological communication pathway and hijacked it for its own benefit. </p>
<p>So if the patient’s pancreatic cancer was using such a resilient network to its advantage, how did McGuire’s patient survive the onslaught?</p>
<h2>Restricting the evil</h2>
<p>The answer turned out to be quite simple. The <a href="http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1031521">strategy</a> is like that used to control the spread of terrorism – surround a small local group of fundamentalists with a large number of non-fundamentalists who do not support their beliefs or missions. The patient’s cancer – although it had spread to several organs – was stuck in environments that did not promote cancer. The cancer cells were surrounded by enough normal cells that the cancer was not able to “convert” the normal cells.</p>
<p>Next, McGuire wanted to see how this approach of network analysis could help her suggest better treatments for the oncologist. </p>
<p>Typical cancer treatments involve drugs or radiation that target cells that have turned rogue. In more extreme circumstances, surgery is used. Recently, another strategy that has become popular is <a href="http://www.sciencemag.org/content/342/6165/1432.full-title=Cancer">cancer immunotherapy</a>, which involves activating the body’s own immune system to do the fighting. </p>
<p>What McGuire found was that cancer had already taken over the patient’s immune system. Using immunotherapy could over-activate the immune system causing it to start attacking body’s normal cells. This sort of auto-immune response could prove dangerous. So, although McGuire’s network analysis hasn’t provided new treatments just yet, it can be used to eliminate treatments which should not be used.</p>
<p>So although the connection seems far-fetched, McGuire shows that we can learn from the tactics of terrorist organisations ways to tackle cancer. Before we can find reliable solutions, however, more detailed studies will be needed. Only then can we start to see the possible therapeutic advantages of network analysis in the long-standing “war on cancer”.</p><img src="https://counter.theconversation.com/content/31658/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mohit Kumar Jolly 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>There may seem to be no connection between terrorism and cancer. But that is an oversight. If considered closely, it is easy to see that both exhibit loss of control present in “normal” conditions and…Mohit Kumar Jolly, Graduate student in Cancer Systems Biology, Rice UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/284202014-06-24T14:16:30Z2014-06-24T14:16:30ZNow we know why drugs don’t work on pancreatic cancer<figure><img src="https://images.theconversation.com/files/52076/original/sktzvvwh-1403613271.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pancreatic cancer with other cells.</span> <span class="attribution"><a class="source" href="http://en.wikipedia.org/wiki/File:Pancreas_adenocarcinoma_(4)_Case_01.jpg">Wikimedia</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>The trouble with treating cancer is that each type has its own quirks. The quirks of pancreatic cancer make it one of the most lethal. The survival period after diagnosis is only four to six months. The main reason is that treatment with drugs – chemotherapy – which has had some success in extending lives for patients with other cancers, fails in the case of pancreatic cancer.</p>
<p>The widely believed reason for this failure has been that in pancreatic cancer, the tissue that surrounds the tumour, called the stroma, blocks the delivery of chemotherapy drugs to the tumour. A new study, published in <a href="http://dx.doi.org/10.1016/j.ccr.2014.04.005">Cancer Cell</a>, questions that logic. It shows that the stroma, instead of supporting tumour progression, inhibits it by activating body’s immune system’s attack on the tumour.</p>
<h2>Tumorous tale</h2>
<p>All tumours are composed of some cancer cells and mostly stroma. But pancreatic cancer is unique – only around 10% of the cells in the tumour are cancer cells. That is the least proportion among all cancer types. The remaining 90% is the stroma consisting of special cells known as myofibroblasts. </p>
<p>Taking clues from this distinctive property of pancreatic cancer, <a href="http://www.ncbi.nlm.nih.gov/pubmed/19460966">previous studies</a> indicated that stroma can act as a physical barrier to the chemotherapy drugs. This finding created a slew of clinical trials for combining chemotherapy with “stromal depletion therapy” – that is, removing the stroma <a href="http://jnci.oxfordjournals.org/content/102/7/448.full">from the tumour</a>. However, these trials <a href="http://www.bizjournals.com/boston/blog/mass-high-tech/2012/01/infinity-pharma-halts-pancreatic-cancer-trial.html">had to be stopped</a> abruptly when patients receiving this combination therapy were found to have an accelerated tumour progression as compared to those that only received chemotherapy. The reasons for this disappointing result remained unclear.</p>
<p>Now, in the new study, Raghu Kalluri and his colleagues at MD Anderson Cancer Center have perhaps found the reason. They propose a mechanism underlying the failure of the clinical trials. </p>
<p>Using mice, who act as proxy for humans, Kalluri and colleagues show that the depletion of myofibroblasts – the major component of stroma – at any stage of pancreatic cancer does not improve the efficiency of chemotherapy. Instead tumours grow more aggressively. This leads to making it difficult for the immune system to control cancer and eventually to higher number of mice deaths. This indicated to Kalluri that perhaps the stroma is inhibiting the tumour instead of promoting.</p>
<p>“We did these experiments thinking that we would show the importance of myofibroblasts and fibrosis in pancreas cancer progression, but the results went completely against that hypothesis,” Kalluri said in a <a href="http://www.eurekalert.org/pub_releases/2014-05/uotm-sti052014.php">statement</a>. </p>
<p>“This supportive tissue that is abundant in pancreatic cancer tumours is not a traitor as we thought but rather an ally that is fighting to the end. It’s a losing battle with cancer cells, but progression is much faster without their constant resistance. It is like having a car with weak yet functioning brakes vs having one with no brakes.”</p>
<h2>Dump me not just yet</h2>
<p>It is not all bad news for stromal depletion therapy, however. Kalluri found that tumours with less stroma had higher levels of CTLA-4, a protein which is responsible for shutting down the immune system response. When these tumours were treated with ipilumimab, a drug that blocks CTLA-4, survival time of the mice increased by 60% as compared to that of the untreated control mice. </p>
<p>This is a shot in the arm for cancer immunotherapy – therapies that enable the body’s immune system to fight cancer directly – which has been considered as the Breakthrough of the Year 2013 by the journal <a href="http://www.sciencemag.org/content/342/6165/1432.summary">Science</a>. This sort of therapy might be more effective for pancreatic cancer patients with relatively less stroma in their tumours. Or a combination of immunotherapy and stromal depletion therapy might be more effective for pancreatic cancer patients with dense stroma, which is usually the case.</p>
<p>The development offers hope for a disease in which only seven out of 100 patients survive for five years after being diagnosed. For managing pancreatic cancer treatment better, rapid progress in its earlier diagnosis is essential.</p><img src="https://counter.theconversation.com/content/28420/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mohit Kumar Jolly 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 trouble with treating cancer is that each type has its own quirks. The quirks of pancreatic cancer make it one of the most lethal. The survival period after diagnosis is only four to six months. The…Mohit Kumar Jolly, Graduate student in Cancer Systems Biology, Rice UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/237432014-02-27T15:19:01Z2014-02-27T15:19:01ZCharity campaigns may cause outrage, but shock sells<figure><img src="https://images.theconversation.com/files/42667/original/rt5d5qnf-1393506432.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We can't always see no evil.</span> <span class="attribution"><a class="source" href="http://www.flickr.com/photos/alisonlongrigg/3503494291/sizes/l/">Alicakes</a></span></figcaption></figure><p>A campaign for Pancreatic Cancer Action recently stirred up controversy over advertising “shock tactics”. In the advert, genuine sufferers of the disease stated to camera that “I wish I had testicular cancer” or “I wish I had breast cancer”. The implication was that those afflictions were preferable to the particularly deadly pancreatic form.</p>
<p>Twitter was particularly aghast at the inference that one type of cancer was desirable to another and the Daily Mail duly printed the sentiments expressed online. The campaign was “offensive, repugnant and hurtful to all cancer victims and their families” as well as being “insensitive to those with breast cancer and who have lost loved ones to it”. </p>
<p>Other charities were equally incensed. Chris Askew, CEO of Breakthrough Breast Cancer, <a href="http://www.mirror.co.uk/news/uk-news/pancreatic-cancer-wish-campaign-outrage-3116014">said</a>: “We strongly dispute any message which suggests that one type of cancer is preferable to another.” </p>
<p>Now, the <a href="http://www.bbc.co.uk/news/health-26355420">death of Kerry Harvey</a>, one of the faces of the campaign, has reawakened the debate. Was Pancreatic Cancer Action right to utilise a dying woman for shock value?</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/IDU1XEAWkxE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Pancreatic Cancer Action.</span></figcaption>
</figure>
<h2>Shocking history</h2>
<p>Shock advertising of this sort is not new to charities. Children’s welfare organisation Bernardo’s has form in this area. In 1999, it ran <a href="http://www.thirdsector.co.uk/Communications/article/1188136/change-makers-barnardos/">a campaign</a> using images of very young babies appearing to inject heroin, while in 2003 it ran <a href="http://www.theguardian.com/media/2003/nov/24/advertising2">poster campaigns</a> depicting a new born baby with a cockroach emerging from its mouth. The intention was to show the potentially miserable and alarming futures faced by vulnerable and disadvantaged young people from the start of their lives. And no one could dispute the arresting and disturbing potency of the imagery. </p>
<p>Moving forward, in 2012 St John’s ambulance showed the journey of a cancer sufferer’s life from diagnosis to recovery only to see him, through his daughter’s eyes, die from an unrelated <a href="http://www.youtube.com/watch?v=sC7zfgCXQFs">choking accident</a>at a barbecue. The message was that knowledge of first aid could save 140,000 lives each year – the same number who die from cancer. It became the <a href="http://www.theguardian.com/voluntary-sector-network/2013/nov/19/charity-shock-tactics-do-they-work">10th most complained about</a> television advertisement of the year.</p>
<p>Clearly, charities have been allowed a certain amount of “leeway” in using content some may consider offensive, partly because of the seriousness of the subject matter and the importance of raising awareness. In the last few years, though, concerns have been raised about the increasing use of disturbing and emotive imagery to elicit a response. As a result the Advertising Standards Authority (ASA) has agreed to put <a href="http://www.asa.org.uk/News-resources/Hot-Topics/Charity-ads.aspx">more checks and balances</a> in place when assessing complaints about charity and public service ads. Pancreatic Cancer Action may face an investigation after the ASA received <a href="http://www.theguardian.com/media/2014/feb/25/pancreatic-cancer-action-ad-investigation-complaints-asa">118 complaints</a>.</p>
<p>So why do charities resort to shock tactics? The answer is simple. The more disturbing or emotive the message, the more likely it is to bring forth response. And while an audience may express disgust or revulsion, that does not necessarily translate into a lack of support for a particular cause. As Lindsay Gormley, assistant director of marketing at Bernardo’s, <a href="http://www.thirdsector.co.uk/news/1143700/Public-feels-charity-adverts-go-far-says-survey-regulator">puts it</a>:</p>
<blockquote>
<p>Barnardo’s has a history of hard-hitting advertising that brings [the gravity of the situation] to life in a powerful and emotional way … For the vast majority of viewers the messages are clear, and as a result we see a substantial increase in people wanting to support Barnardo’s work.</p>
</blockquote>
<p>Team Darwin, the agency behind, the “I wish I had breast cancer” campaign argues, perhaps predictably, that other charities should be emboldened to follow their lead. According to chief creative <a href="http://www.thedrum.com/opinion/2014/02/12/controversial-i-wish-i-had-breast-cancer-campaign-creator-why-charities-need-be">Greg Phitidis</a>: </p>
<blockquote>
<p>within 48 hours of the campaign breaking, global news channels were advising on signs and symptoms. And our client has been invited to Westminster to discuss research and funding with MPs, something that would never have happened if we’d taken the edge off the campaign.</p>
</blockquote>
<p>The link between Team Darwin’s campaign and parliamentary involvement in this instance is undeniable. However, it would be foolish not to acknowledge that in certain cases the danger is that the shock value of an ad becomes the currency of debate rather than the issue it is trying to promote. </p>
<p>In the case of the St John’s ambulance campaign, the point was to raise awareness and spur the public into action. In these cases, there is some concern that shock advertising, while improving profile, can alienate the intended audience. To take one example, Cancer Research UK explored a range of options when looking at how best to encourage people to visit their GP upon discovering an early symptom of cancer. “We found that using a hard-hitting approach in that instance didn’t really work because people are very afraid,” <a href="http://www.marketingweek.co.uk/analysis/essential-reads/are-shock-tactics-back/4005401.article">says marketing manager Abigail Brown</a>. “If someone thinks they might have cancer or has a symptom, they’re likely to try to push it out of their mind.”</p>
<p>For most charities though, the bottom line is raising enough money to continue to operate effectively. Fundraising can depend on publicity generated, and charities are under pressure to stand out and be noticed in the 24/7 culture of fleeting images and rolling news. </p>
<p>When ActionAid toned down its imagery of extreme poverty in the face of criticism, campaigning became “<a href="http:/www.theguardian.com/voluntary-sector-network/2013/nov/19/charity-shock-tactics-do-they-work.">unsuccessful from a fundraising viewpoint</a>”. For Greg Phitidis, the man behind “I wish I had breast cancer”, the UK is suffering from cause fatigue and the “<a href="http://www.thedrum.com/opinion/2014/02/12/controversial-i-wish-i-had-breast-cancer-campaign-creator-why-charities-need-be">bold approach</a>” is the only way forward.</p><img src="https://counter.theconversation.com/content/23743/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Jewell 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>A campaign for Pancreatic Cancer Action recently stirred up controversy over advertising “shock tactics”. In the advert, genuine sufferers of the disease stated to camera that “I wish I had testicular…John Jewell, Director of Undergraduate Studies, School of Journalism, Media and Cultural Studies, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/103272012-10-25T04:56:12Z2012-10-25T04:56:12ZBeginning of the end for cancer?<figure><img src="https://images.theconversation.com/files/16886/original/x452w76d-1351132776.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The consortium's work means cancer’s reign as one of our most devastating diseases may be over sooner rather than later.</span> <span class="attribution"><span class="source">shutterstock.com</span></span></figcaption></figure><p>The first results of the most comprehensive genetic survey of cancer ever to be undertaken by an international consortium of researchers have just started to come in. The consortium is mapping mutations of different types of cancers with the aim of better targetting treatment.</p>
<p>The findings for pancreatic cancer were published in the <a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11547.html">peer-reviewed journal Nature</a> this morning. Professor Andrew Biankin from the Kinghorn Cancer Centre at the Garvan Institute of Medical Research and I led this survey, which sequenced the genomes of 100 pancreatic tumours from Australians and North Americans and compared them to normal tissue.</p>
<h2>Pancreatic cancer and genome mapping</h2>
<p>Pancreatic cancer is not the most common cancer to afflict Australians. It’s actually tenth on the list, but it kills more people than melanoma. And fewer than 5% of patients diagnosed with pancreatic cancer will survive more than five years. It’s one of the few cancers for which survival rates have not increased over the past 40 years.</p>
<p>The problem is that it’s a complex cancer that usually isn’t detected until it has spread. Clearly, there’s a lot of scope to better understand this disease and how we can treat it more effectively.</p>
<p>Our project is part of the International Cancer Genome Consortium (ICGC), which has brought labs across the world together to sequence the genomes of 50 different types of tumours.</p>
<p>Cancer arises from the accumulation of genetic damage. You can compare it to randomly deleting files from a hard drive. Some files, if deleted, won’t make any difference to the functioning of the computer at all, while others are vital. If these files are deleted, the computer will cease functioning.</p>
<p>The cancer genome consortium is seeking to identify these mutations – the ones that cause a healthy cell to turn cancerous – and make this data freely available to scientists and clinicians. It’s been 12 years since the draft copy of the human genome was made public, and in that time, sequencing technology has made incredible advances.</p>
<p>The Human Genome Project took over a decade and cost over US$2 billion. In our laboratories at the University of Queensland’s Institute for Molecular Bioscience, we can sequence a genome in a matter of days for a few thousand dollars.</p>
<p>Across the 100 pancreatic cancers we studied, we identified over 2,000 mutations, a small number of which appear to be the genes that really drive the formation of tumours. We’ve also learnt that, as with many other types of cancer, pancreatic cancer is actually an umbrella term.</p>
<p>This means there are many sub-types of pancreatic cancer, each with different prognoses and different potential treatments. These differences can’t be seen with a microscope; sequencing is required to pinpoint what sets one tumour apart from the next.</p>
<h2>With patients, for patients</h2>
<p>This research, indeed that of the whole of the International Cancer Genome Consortium, wouldn’t have been possible without the cancer patients who donated their samples. They did so because they wanted to make a difference, and that’s the overarching aim for this project.</p>
<p>Our findings emphasise the importance of treating patients as individuals, because when it comes to cancer types and treatments, one size most definitely does not fit all.</p>
<p>Our research aims to take the guesswork out of chemotherapy by allowing doctors to match the genetics of a person’s tumour with a treatment. We found some patients with mutations in genes that are commonly associated with other types of cancer, such as breast cancer.</p>
<p>The good news for these people is that some of these genes are already treatable with drugs and, in some cases, we were able to direct their doctors to treat them with the correct drug. Next year, we’ll begin clinical trials to assess the benefit of using this method of treating patients versus standard chemotherapy in advanced pancreatic ductal adenocarcinoma.</p>
<p>This type of personalised medicine, where the individual is treated rather than the disease, is the future of medicine. It probably won’t be too many years before it will be standard procedure to have your diseased cells sequenced and your genetic make-up examined to determine treatment.</p>
<p>Of course, there’s more work to be done, but we hope our research can make a difference sooner rather than later in the lives of those affected by pancreatic cancer. </p>
<p>And with scientists and clinicians from around the world joining forces through the International Cancer Genome Consortium, we hope that cancer’s reign as one of our most devastating diseases will be over sooner rather than later.</p><img src="https://counter.theconversation.com/content/10327/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sean Grimmond receives funding from the National Health and Medical Research Council, Australian Research Council, and Cancer Council NSW.</span></em></p>The first results of the most comprehensive genetic survey of cancer ever to be undertaken by an international consortium of researchers have just started to come in. The consortium is mapping mutations…Sean Grimmond, Professorial Research Fellow, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.