tag:theconversation.com,2011:/africa/topics/metastasis-8523/articlesMetastasis – The Conversation2023-11-01T12:35:53Ztag:theconversation.com,2011:article/2156982023-11-01T12:35:53Z2023-11-01T12:35:53ZCancer has many faces − 5 counterintuitive ways scientists are approaching cancer research to improve treatment and prevention<figure><img src="https://images.theconversation.com/files/553918/original/file-20231016-15-3osk1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2700%2C1758&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cancer cells don't follow the typical rules that allow a multicellular collective to function.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Cancer_cells_(1).jpg">Dr. Cecil Fox/National Cancer Institute</a></span></figcaption></figure><p>How researchers conceptualize a disease informs how they treat it. Cancer is often described as uncontrollable cell growth triggered by genetic damage. But cancer can also be seen from angles that emphasize mathematics, evolutionary game theory and physics, among others.</p>
<p>Molecular biology has brought significant advances in making it possible to live with cancer as a chronic illness rather than a fatal disease. Alternative frameworks, however, can offer scientists additional insights on how to prevent tumors from spreading throughout the body and becoming resistant to treatment.</p>
<p>Here are a few unconventional lenses through which researchers are viewing cancer with fresh eyes, drawn from The Conversation’s archives.</p>
<h2>1. Evolution and natural selection of cancer</h2>
<p>The body is far from a wonderland for cells. Each individual cell competes against trillions of others for finite space and nutrients. If they’re able to cooperate in an orderly enough fashion, sharing resources and dividing labor, the collective functions effectively. Cancer cells, however, <a href="https://theconversation.com/microbes-in-your-food-can-help-or-hinder-your-bodys-defenses-against-cancer-how-diet-influences-the-conflict-between-cell-cooperators-and-cheaters-195810">cheat the system</a>: They hog resources, take up as much space as possible and <a href="https://theconversation.com/what-are-hela-cells-a-cancer-biologist-explains-169913">refuse to die</a>.</p>
<p>In this way, cancer can be thought of as <a href="https://theconversation.com/every-cancer-is-unique-why-different-cancers-require-different-treatments-and-how-evolution-drives-drug-resistance-199249">an evolutionary disease</a> – these are cells that have developed the genetic mutations to outcompete their neighbors, and subsequent cell generations inherit this survival advantage. Cancer cells benefit at the expense of the collective until the entire organism collapses.</p>
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<a href="https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of pancreas tumor with multicolored cell subgroups" src="https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=458&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=458&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=458&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=575&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=575&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554078/original/file-20231016-27-4u7mpn.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>
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<span class="caption">Most tumors are made of many different kinds of cancer cells, as shown in this pancreatic cancer sample from a mouse.</span>
<span class="attribution"><a class="source" href="https://visualsonline.cancer.gov/details.cfm?imageid=10654">Ravikanth Maddipati/Abramson Cancer Center at the University of Pennsylvania via National Cancer Institute</a></span>
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<p>Oncologist <a href="https://cancer.psu.edu/researchers/individual/-/researcher/5B6500F63D6A38DBE0540010E056499A/monika-joshi-md-mrcp">Monika Joshi</a> and pathologists <a href="https://cancer.psu.edu/researchers/individual/-/researcher/5F6E820FF5C14A2DE0540010E056499A/joshua-warrick-md">Joshua Warrick</a> and <a href="https://scholar.google.com/citations?user=YEqQHkIAAAAJ&hl=en">David DeGraff</a> believe that understanding evolution is key to understanding cancer. Screening programs are effective, for example, because removing a nascent tumor is easier than treating one that has evolved the ability to spread. Cancer cells likewise become resistant to treatments because they’re pushed to further evolve to survive.</p>
<p>Some researchers are applying the principles of evolutionary game theory to <a href="https://theconversation.com/cancers-are-in-an-evolutionary-battle-with-treatments-evolutionary-game-theory-could-tip-the-advantage-to-medicine-17017">reduce treatment resistance</a> and optimize <a href="https://theconversation.com/cancer-in-kids-is-different-from-cancer-in-grown-ups-figuring-out-how-could-lead-to-better-pediatric-treatments-212738">therapies for children</a>.</p>
<p>“The fight against cancer is a fight against evolution, the fundamental process that has driven life on Earth since time immemorial,” they wrote. “This is not an easy fight, but medicine has made tremendous progress.”</p>
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Read more:
<a href="https://theconversation.com/every-cancer-is-unique-why-different-cancers-require-different-treatments-and-how-evolution-drives-drug-resistance-199249">Every cancer is unique – why different cancers require different treatments, and how evolution drives drug resistance</a>
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<h2>2. Fluid mechanics of cancer</h2>
<p>As much as cancer is a disease that respects no boundaries, tumor cells are still shaped by their environment. Unlike healthy cells that take the hint when their presence isn’t wanted, however, tumor cells not only <a href="https://theconversation.com/stopping-the-cancer-cells-that-thrive-on-chemotherapy-research-into-how-pancreatic-tumors-adapt-to-stress-could-lead-to-a-new-treatment-approach-197768">survive but thrive in stressful conditions</a>. Isolated cancer cells able to adapt to harsh settings are the ones that establish metastatic colonies and become resistant to treatment.</p>
<p>While researchers have focused on how biochemical signals direct cells to move from one location to another, a cell’s physical environment also affects where it migrates. Mechanical engineer <a href="https://scholar.google.com/citations?user=nKmJNpQAAAAJ&hl=en">Yizeng Li</a> found that a cell’s “solid” and “fluid” surroundings influence its movement.</p>
<p>Cancer cells encounter varying degrees of fluid viscosity, or thickness, as they travel through the body. Li and her team found that breast cancer cells counterintuitively move faster in high viscosity environments by changing their structure. This meant that fluid viscosity serves as a <a href="https://theconversation.com/how-cancer-cells-move-and-metastasize-is-influenced-by-the-fluids-surrounding-them-understanding-how-tumors-migrate-can-help-stop-their-spread-195792">mechanobiological cue for cancer cells to metastasize</a>.</p>
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<a href="https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Animation comparing two fluids with lower and higher viscosity." src="https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=463&fit=crop&dpr=1 600w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=463&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=463&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=582&fit=crop&dpr=1 754w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=582&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=582&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">The blue fluid on the left has a lower viscosity relative to the orange fluid on the right.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/File:Viscosities.gif">Synapticrelay/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>“Cancer patients usually don’t die from the original source of the tumor but from its spread to other parts of the body,” Li wrote. “Understanding how fluid viscosity affects the movement of tumor cells could help researchers figure out ways to better treat and detect cancer before it metastasizes.”</p>
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Read more:
<a href="https://theconversation.com/how-cancer-cells-move-and-metastasize-is-influenced-by-the-fluids-surrounding-them-understanding-how-tumors-migrate-can-help-stop-their-spread-195792">How cancer cells move and metastasize is influenced by the fluids surrounding them – understanding how tumors migrate can help stop their spread</a>
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<h2>3. Inflammation link to cardiovascular disease</h2>
<p>Apart from being leading causes of death around the world, cardiovascular disease and cancer may not initially seem to have much in common. The many risk factors they share, however – like poor diet, smoking and chronic stress – coalesce with chronic inflammation: persistent, low-grade activation of the immune system can damage cells in ways that encourage either disease to develop. </p>
<p>For biomedical engineer <a href="https://scholar.google.com/citations?user=wD6KbXkAAAAJ&hl=en">Bryan Smith</a>, the developmental parallels between these diseases signal they could be <a href="https://theconversation.com/could-a-single-drug-treat-the-two-leading-causes-of-death-in-the-us-cancer-and-cardiovascular-disease-205461">treated at the same time</a>.</p>
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<figcaption><span class="caption">Nanoparticles can ‘eat’ the plaques that cause heart disease.</span></figcaption>
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<p><a href="https://theconversation.com/drugs-4-essential-reads-on-how-theyre-made-how-they-work-and-how-context-can-make-poison-a-medicine-192590">Drugs can be repurposed</a> to target diseases for which they weren’t originally designed. Certain drugs, for example, can direct immune cells called macrophages to consume both cancer cells and the cellular debris that contribute to cardiovascular plaques.</p>
<p>“As basic science discovers other molecular parallels between these diseases, patients will be the beneficiaries of better therapies that can treat both,” wrote Smith.</p>
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Read more:
<a href="https://theconversation.com/could-a-single-drug-treat-the-two-leading-causes-of-death-in-the-us-cancer-and-cardiovascular-disease-205461">Could a single drug treat the two leading causes of death in the US: cancer and cardiovascular disease?</a>
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<h2>4. Mathematics of cancer</h2>
<p>In certain contexts, math has unique strengths in <a href="https://theconversation.com/big-bang-of-numbers-the-conversations-book-club-explores-how-math-alone-could-create-the-universe-with-author-manil-suri-213690">describing the natural world</a>. For instance, epigenetics – where and when genes are turned on or off – plays as much a role in cancer progression as direct changes to the genetic code. Epigenetic changes can alter healthy cells to the point of losing their normal form and function. But the randomness of these changes makes it difficult to tease out pathological from normal genetic activity.</p>
<p>A mathematical concept called stochasticity – or how the randomness of the steps of a process influences how predictable its outcome will be – lends a logical framework to the <a href="https://theconversation.com/cancer-evolution-is-mathematical-how-random-processes-and-epigenetics-can-explain-why-tumor-cells-shape-shift-metastasize-and-resist-treatments-199398">epigenetic changes contributing to cancer</a>, clarifying when healthy cells rapidly develop into tumor cells. </p>
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<figcaption><span class="caption">Twins sharing the exact same genome can develop in completely different ways because of epigenetics.</span></figcaption>
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<p>Stochasticity is commonly used to study stock market behavior and epidemic disease spread, and researchers quantify it by examining the degree of uncertainty, or entropy, of a particular outcome. Identifying high entropy areas in the genome could offer another approach to cancer detection and drug design.</p>
<p>Cancer geneticist <a href="https://scholar.google.com/citations?user=tbj-LpcAAAAJ&hl=en">Andrew Feinberg</a> has been using entropy to quantitatively describe the epigenetics of cancer. He and his colleagues found that high entropy regions of the genome in the skin become even more entropic with sun damage, increasing the chance of developing cancer. This offers a potential explanation for why cancer risk significantly increases with age.</p>
<p>“Epigenetic entropy shows that you can’t fully understand cancer without mathematics,” Feinberg wrote. “Biology is catching up with other hard sciences in incorporating mathematical methods with biological experimentation.”</p>
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Read more:
<a href="https://theconversation.com/cancer-evolution-is-mathematical-how-random-processes-and-epigenetics-can-explain-why-tumor-cells-shape-shift-metastasize-and-resist-treatments-199398">Cancer evolution is mathematical – how random processes and epigenetics can explain why tumor cells shape-shift, metastasize and resist treatments</a>
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<h2>5. A public health issue</h2>
<p>Cancer is a disease that develops in an individual, but its socially derived causes and societal-wide effects are hardly limited to a single person.</p>
<p>Take the case of lung cancer. It is stigmatized as a disease brought on by poor lifestyle choices – a consequence of a personal decision to use tobacco products. But as thoracic oncologist <a href="https://doctors.umiamihealth.org/provider/Estelamari+Rodriguez/1257821">Estelamari Rodriguez</a> noted, the face of lung cancer has changed.</p>
<p>“Over the past 15 years, more women, never-smokers and younger people are being diagnosed with lung cancer,” she wrote. While lung cancer rates have significantly decreased for men, they have <a href="https://theconversation.com/lung-cancer-rates-have-decreased-for-the-marlboro-man-but-have-risen-steeply-for-nonsmokers-and-young-women-an-oncologist-explains-why-197581">substantially risen for women</a> around the world. Despite being the leading cause of cancer death among women, screening rates remain low compared with other cancers.</p>
<p>More broadly, cancer symptoms are often unrecognized or misdiagnosed, not only <a href="https://theconversation.com/ovarian-cancer-is-not-a-silent-killer-recognizing-its-symptoms-could-help-reduce-misdiagnosis-and-late-detection-181415">for women</a> but also for many marginalized populations, including <a href="https://theconversation.com/biopsies-confirm-a-breast-cancer-diagnosis-after-an-abnormal-mammogram-but-structural-racism-may-lead-to-lengthy-delays-185824">people of color</a>, <a href="https://theconversation.com/doctors-often-arent-trained-on-the-preventive-health-care-needs-of-gender-diverse-people-as-a-result-many-patients-dont-get-the-care-they-need-191933">transgender patients</a> and <a href="https://theconversation.com/how-obamacare-has-helped-poor-cancer-patients-85306">the uninsured</a>.</p>
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<figcaption><span class="caption">An increasing number of lung cancer diagnoses are among people who never smoked.</span></figcaption>
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<p>These disparities are due in part to biases in medical education and <a href="https://theconversation.com/yes-black-patients-do-want-to-help-with-medical-research-here-are-ways-to-overcome-the-barriers-that-keep-clinical-trials-from-recruiting-diverse-populations-185337">clinical research</a> that fail to prepare clinicians to care for the diversity of patients they’ll encounter. <a href="https://theconversation.com/the-next-attack-on-the-affordable-care-act-may-cost-you-free-preventive-health-care-166087">Tenuous access to preventive care</a> and disproportionate <a href="https://theconversation.com/arsenic-contamination-of-food-and-water-is-a-global-public-health-concern-researchers-are-studying-how-it-causes-cancer-200689">exposure to carcinogens</a> among certain populations compound these inequities.</p>
<p>The purview of cancer goes far beyond a single discipline. It takes a village of researchers, policymakers and patient advocates to achieve effective and accessible cancer care for all.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/lung-cancer-rates-have-decreased-for-the-marlboro-man-but-have-risen-steeply-for-nonsmokers-and-young-women-an-oncologist-explains-why-197581">Lung cancer rates have decreased for the Marlboro Man, but have risen steeply for nonsmokers and young women – an oncologist explains why</a>
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From math to evolutionary game theory, looking at cancer through different lenses can offer further insights on how to approach treatment resistance, metastasis and health disparities.Vivian Lam, Associate Health and Biomedicine EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134462023-09-20T21:28:41Z2023-09-20T21:28:41ZObesity is a dangerous disease that shares key features with cancer<figure><img src="https://images.theconversation.com/files/549385/original/file-20230920-19-5q8kcd.jpg?ixlib=rb-1.1.0&rect=3851%2C14%2C5663%2C4180&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Obesity is itself a disease, in addition to contributing to the onset and progression of other conditions such as diabetes, heart attack and stroke.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/obesity-is-a-dangerous-disease-that-shares-key-features-with-cancer" width="100%" height="400"></iframe>
<p>Although obesity has been <a href="https://doi.org/10.1038/ijo.2008.247">recognized as a disease by the World Health Organization (WHO)</a> since 1948, its identity as a disease may not be widely perceived the same way as other health conditions. </p>
<p>People living with obesity are less <a href="https://doi.org/10.1007/s13679-021-00444-y">likely to receive dedicated care for that condition</a>, in contrast to patients with other diseases, such as cancer. However, obesity and cancer have several similarities. This is of <a href="https://www.worldobesityday.org/">global crucial importance</a>, given the dramatic increase in numbers of affected adults and children, <a href="https://data.worldobesity.org/country/canada-36/">including in Canada</a>.</p>
<h2>Obesity is a disease</h2>
<p>Like cancer, or other medically recognized diseases, obesity should be seriously considered as such by public opinion. Not only is obesity itself a disease, but it can also contribute to the onset and progression of <a href="https://doi.org/10.1177/2042018820934955">cancer and other diseases</a>, such as <a href="https://doi.org/10.1155/2018/3407306">diabetes, atherosclerosis, heart attack and stroke</a>.</p>
<p>The disease of obesity affects people in several ways:</p>
<p><strong>Mechanically:</strong> Obesity imposes an excessive <a href="https://www.health.harvard.edu/pain/why-weight-matters-when-it-comes-to-joint-pain">pressure on the bones and the joints</a>, as well as internal organs. It can also <a href="https://www.sleepfoundation.org/sleep-apnea/weight-loss-and-sleep-apnea">potentially cause airway obstruction</a> that can lead to obstructive sleep apnea.</p>
<p><strong>Biologically:</strong> <a href="https://doi.org/10.3389/fimmu.2022.907750">Obesity can lead to osteoarthritis</a>, for example, and it presents with <a href="https://doi.org/10.1172/JCI92035">inflammation</a> and <a href="https://doi.org/10.3390/ijms21103570">dysregulated secretions</a> by dysfunctional fat tissue cells. </p>
<p>Obesity can also result in <a href="https://doi.org/10.1172/JCI81507%22%22">abnormal fat deposits on vital organs</a>, which seriously alters the whole organism’s <a href="https://www.britannica.com/science/homeostasis">homeostasis</a>, or biological stability.</p>
<p><strong>Psychologically:</strong> <a href="https://doi.org/10.1111/scs.12756">Patients with obesity may face difficulties in accomplishing daily activities</a>; even simple things such as tying their shoelaces may be a challenge. This is further worsened by <a href="https://doi.org/10.1016/j.eclinm.2022.101464">social media’s deep influence</a> and promotion of a presumed “ideal” unrealistic body shape image, which stigmatizes patients with obesity. </p>
<p>There is also evidence that obesity is accompanied by <a href="https://doi.org/10.1007/s12272-019-01138-9">brain inflammation</a> and increased risk of mental health conditions such as major <a href="https://doi.org/10.1038/s41380-018-0017-5">depressive disorder</a> and <a href="https://doi.org/10.1007/s40211-019-0302-9">anxiety</a>.</p>
<h2>Common characteristics of obesity and cancer</h2>
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<img alt="Illustration with two human figures representing cancer and obesity flanking a list of common factors: Metastatic, Recurrent, Progressive and Multifactorial" src="https://images.theconversation.com/files/548475/original/file-20230915-23-edvy8n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548475/original/file-20230915-23-edvy8n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=503&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548475/original/file-20230915-23-edvy8n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=503&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548475/original/file-20230915-23-edvy8n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=503&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548475/original/file-20230915-23-edvy8n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=633&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548475/original/file-20230915-23-edvy8n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=633&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548475/original/file-20230915-23-edvy8n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=633&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">As a disease, obesity shares many common features with cancer.</span>
<span class="attribution"><span class="source">(Besma Boubertakh, using Biorender.com and Mindthegraph.com)</span></span>
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<p>Obesity shares several major features with cancer:</p>
<p><strong>Multifactorial grounds:</strong> Both diseases present no single known cause, which can make prevention and treatment challenging. </p>
<p>Obesity is not simply due to individual lifestyles of high-calorie consumption or low levels of physical exercise, since the balance between energy intake and expenditure can be tipped in either direction by <a href="https://doi.org/10.1007/s00261-012-9862-x">genetics, the environment as well as other factors that are not completely understood</a>.</p>
<p><strong>Metastasis:</strong> <a href="https://doi.org/10.3390/cells11121872">Like cancer, obesity can involve metastases</a>, meaning that the disease can spread to other parts of the body. </p>
<p>In the case of obesity, this takes the form of ectopic fat deposits, which occur when adipose (fat) tissue cannot store all of the excess <a href="https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186">triglycerides</a>, a type of lipid, or fat. Triglycerides then accumulate beyond their normal locations, including around organs. In obesity, fat can be deposited on the heart, the liver, in blood vessels and <a href="https://doi.org/10.1113/jphysiol.2012.239491">even the brain</a>. These deposits can alter vital organ function and have devastating effects on an individual’s health.</p>
<p><strong>Progressive development and stages:</strong> <a href="https://doi.org/10.1155/2015/619734">Obesity</a>, like <a href="https://doi.org/10.1038/s41568-020-00300-6">cancer,</a> can develop progressively to reach advanced harmful stages. One of the reasons why people may consider obesity as a less serious illness than cancer is that they may pay more attention to the stages of cancer. </p>
<p>In fact, both obesity and cancer might advance progressively in the absence of proper diagnosis and intervention. However, deaths that originate in obesity are most often attributed to potential consequent diseases (such as cardiovascular ischemic events or even cancer) and neglect the pivotal impact of obesity.</p>
<figure class="align-center ">
<img alt="A red yo-yo with a measuring tape instead of a string" src="https://images.theconversation.com/files/549432/original/file-20230920-29-30f3tt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/549432/original/file-20230920-29-30f3tt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/549432/original/file-20230920-29-30f3tt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/549432/original/file-20230920-29-30f3tt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/549432/original/file-20230920-29-30f3tt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/549432/original/file-20230920-29-30f3tt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/549432/original/file-20230920-29-30f3tt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Many people with obesity struggle to control weight regain following weight loss, a phenomenon often called ‘yo-yo’ effect. However, recurrence is a better term that should replace yo-yo, since it more seriously emphasizes that obesity is far from a game.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p><strong>Recurrence:</strong> Those who recover from obesity can experience recurrence of the disease. A good example is seen in <em>The Biggest Loser</em> TV series. <a href="https://www.health.harvard.edu/diet-and-weight-loss/lessons-from-the-biggest-loser">Contestants who lost weight</a> on the show <a href="https://doi.org/10.1002/oby.21538">later regained it</a>.</p>
<p>Obesity recurrence is often referred to as “yo-yo” effect. However, “recurrence” is a better term that should replace yo-yo, since it more seriously emphasizes that obesity is far from a game. In fact, certain patients struggle deeply to curb uncontrollable weight regain.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-obesity-epidemic-is-fuelled-by-biology-not-lack-of-willpower-209121">The obesity epidemic is fuelled by biology, not lack of willpower</a>
</strong>
</em>
</p>
<hr>
<p>As illustrated by the tale of the Emperor’s New Clothes, people’s perceptions can be erroneous. Often, perceptions of obesity do not reflect its serious threats to health. Obesity is scientifically proven to be a disease, and internationally recognized as one. The mirroring of its features with cancer reveals its inherent morbid potential.</p>
<figure class="align-center ">
<img alt="Illustration of a tailor, and a king in his underwear looking in a mirror" src="https://images.theconversation.com/files/549437/original/file-20230920-25-zab88z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/549437/original/file-20230920-25-zab88z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/549437/original/file-20230920-25-zab88z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/549437/original/file-20230920-25-zab88z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/549437/original/file-20230920-25-zab88z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/549437/original/file-20230920-25-zab88z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/549437/original/file-20230920-25-zab88z.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">We need to heed the lesson from the tale of the Emperor’s New Clothes, and recognize the reality of things: obesity is not simply a discomfort but a real disease.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Obesity is a disease because it can cause deterioration of several aspects of health. <a href="https://www.who.int/about/governance/constitution">WHO defines health</a> as “a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity.” </p>
<p>Even though obesity shares numerous morbidity characteristics with cancer, it does not get the same society-wide recognition as a disease, and people with obesity may be less likely to get the help and treatment they need. There is an urgent need to reshape the way obesity is viewed.</p><img src="https://counter.theconversation.com/content/213446/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors receive funding from the Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND; Chairholder Prof. Vincenzo Di Marzo).</span></em></p><p class="fine-print"><em><span>Cristoforo Silvestri receives funding from the Canada First Research Excellence Fund through Sentinelle Nord of Université Laval.</span></em></p>Obesity is a disease that shares several characteristics with cancer, but does not get the same society-wide recognition of its disease status, so people with obesity are less likely to get treatment.Besma Boubertakh, Doctoral student, molecular medicine, Université LavalCristoforo Silvestri, Assistant Professor, Faculty of Medicine, Université LavalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2093712023-08-11T12:38:49Z2023-08-11T12:38:49ZSkin cancer screening guidelines can seem confusing – three skin cancer researchers explain when to consider getting checked<figure><img src="https://images.theconversation.com/files/539388/original/file-20230725-17-v7y631.jpg?ixlib=rb-1.1.0&rect=0%2C8%2C5454%2C3714&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A history of sunburns may put people at greater risk of developing skin cancer.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/young-womans-back-being-examined-at-a-royalty-free-image/166130792?phrase=skin+cancer+screening&adppopup=true">dnberty/iStock via Getty Images Plus</a></span></figcaption></figure><p><em>Protecting oneself from the summer sun and its damaging ultraviolet rays is often not straightforward. And public health messaging around when and how to be screened for skin cancer has become somewhat confusing.</em></p>
<p><em>In April 2023, the U.S. Preventive Services Task Force, an independent national panel of science experts, provided <a href="https://doi.org/10.1001/jama.2023.4342">updated recommendations on skin cancer</a> screening following a <a href="https://doi.org/10.1001/jama.2023.3262">systematic review of existing research</a>. The task force concluded that the evidence does not support annual widespread skin screening of adolescents and adults, but that catching cancers at the earliest stages reduces the risk of death from skin cancer.</em> </p>
<p><em>At first glance, these statements appear conflicting. So The Conversation asked dermatology experts <a href="https://som.cuanschutz.edu/Profiles/Faculty/Profile/7842">Enrique Torchia</a>, <a href="https://som.cuanschutz.edu/Profiles/Faculty/Profile/20820">Tamara Terzian</a> and <a href="https://coloradosph.cuanschutz.edu/resources/directory/directory-profile/Box-Neil-UCD4553">Neil Box</a> to help unravel the task force recommendations, what they mean for the public and how people can minimize their skin cancer risk.</em></p>
<h2>How common is skin cancer in the US?</h2>
<p>Skin cancer affects about 6 million Americans yearly, according to the Centers for Disease Control and Prevention. This number is <a href="https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2023-cancer-facts-figures.html">more than all other types of cancers combined</a>. </p>
<p><a href="https://medschool.cuanschutz.edu/colorado-cancer-center/for-patients-families/cancers-we-treat/skin-cancer">Basal cell carcinoma and squamous cell carcinoma</a> – collectively known as keratinocyte cancers – account for more than <a href="https://doi.org/10.1016/j.jaad.2021.03.109">97% of skin cancer cases</a>, but invasive melanomas cause the most deaths. Keratinocyte cancers arise from basal cells and the more differentiated squamous cells in the epidermis – the top layer of skin – whereas melanoma comes from melanocytes found at the junction of the epidermis and the dermis, or middle layer. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram showing human skin layers." src="https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/542208/original/file-20230810-21547-6nm4f8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=471&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The majority of skin cancers arise from cells within the epidermis, or top layer, of the skin.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/human-skin-layers-royalty-free-illustration/1149397551?phrase=dermis+layers&adppopup=true">About time/ iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>Unlike normal cells, skin cancer cells grow without constraints, acquiring the ability to invade down into the dermis.</p>
<p>Invasive melanomas are classified by stages 1 through 4. The higher the number, the more invasive the tumor is into the dermis and to other organs of the body in <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/metastasis">a process called metastasis</a>. </p>
<h2>What are the main causes of skin cancer?</h2>
<p>Overexposure to ultraviolet rays causes the majority of skin cancers. Both light- and dark-skinned people <a href="https://www.aad.org/media/stats-skin-cancer">can get skin cancer</a>, but light-skinned individuals have a greater risk. Those with light skin, light or red hair, or with numerous moles, are more susceptible to skin damage and severe burns by ultraviolet rays. Darker-skinned individuals produce more of the <a href="https://my.clevelandclinic.org/health/body/22615-melanin">protective pigment called melanin</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cartoon of a young female on the left before sunburn and on the right with a sunburned face, with sunrays hitting an illustration of the skin layers in the middle." src="https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/542237/original/file-20230810-23008-qfmzoe.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">Overexposure to UV light damages skin, causing sunburns and stimulating melanocytes to make melanin, the protective pigment that darkens skin during tanning. Sunscreen can protect skin from UV damage.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/care-before-after-image-royalty-free-illustration/609443652">chombosan/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>Tanning serves as the body’s protective response to skin damage from ultraviolet rays, stimulating melanocytes to <a href="https://doi.org/10.1111/exd.14260">produce melanin</a>. People who use tanning beds are at a higher risk of skin damage and skin cancers. This is why the American Academy of Dermatology and others <a href="https://www.aad.org/media/stats-indoor-tanning">recommend avoiding tanning beds</a>. Outdoor workers or those who spend time outdoors recreationally, especially at higher elevation, are exposed to more ultraviolet light. </p>
<p>A history of sunburns also puts people at greater risk of developing skin cancer. Because the damage from ultraviolet, or UV, exposure is cumulative, skin cancer is <a href="https://www.skincancer.org/skin-cancer-information/skin-cancer-facts/">more prevalent in people over 55 years old</a>. </p>
<p>Survivors of skin cancers are also <a href="https://doi.org/10.1111/jdv.12887">more likely to get another cancer</a> in their lifetime. Moreover, those who had a squamous cell carcinoma may be at <a href="https://doi.org/10.1007/s00403-017-1724-5">higher risk of dying from noncancer causes</a>. The reasons for these observations are not well understood but may be linked to inflammation or altered immunity, or both, in skin cancer survivors.</p>
<h2>What is the debate behind screening?</h2>
<p>The ongoing debate revolves around whether more screening reduces the death toll from melanoma. </p>
<p>Since the early 1990s, the incidence of melanoma has risen dramatically in the U.S. This increase may be due in part to more emphasis on early detection. <a href="https://doi.org/10.1056/NEJMsb2019760">More melanomas have been found</a>, particularly those identified at the earliest stage, also known as <a href="https://www.aimatmelanoma.org/stages-of-melanoma/">stage 0</a> or melanoma <em>in situ</em>. </p>
<p>Despite this, the rate of death per capita from melanoma has remained unchanged over the last 40 years. Researchers have <a href="https://doi.org/10.1056/NEJMsb2019760">attributed this fact to overdiagnosis</a>, in which suspicious lesions are diagnosed as early melanomas, even though they may not actually be melanomas or progress to be invasive melanomas, which have <a href="https://www.cancer.org/cancer/types/melanoma-skin-cancer/detection-diagnosis-staging/survival-rates-for-melanoma-skin-cancer-by-stage.html">the worst prognosis</a>. </p>
<p>This observation suggests that widespread screening may result in unnecessary surgical biopsies and increased psychological stress associated with a cancer diagnosis. </p>
<p>However, a recent study published after the task force recommendations showed that patients with melanoma <em>in situ</em> had a slight risk of death from melanoma, but <a href="https://doi.org/10.1001/jamadermatol.2023.1494">lived longer than the average person</a>. The authors speculated that the diagnosis of early stage melanoma resulted in a greater awareness of the patient’s overall health, leading to more health-conscious behavior. So, there may be additional benefits to screening the public. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/UnCUcFJJDSA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Regular self-exams help you catch skin cancer early, when it’s most treatable.</span></figcaption>
</figure>
<h2>What did the task force base its new recommendations on?</h2>
<p>The task force reviewed current and past data on the major types of skin cancers. The expert panel relied in part on the results of a large public <a href="https://doi.org/10.1016/j.jaad.2010.11.016">skin cancer screening program</a> in Germany. This program initially examined 20-year-olds from a single state and subsequently <a href="http://dx.doi.org/10.1136/bmjopen-2015-008158">expanded the program nationwide</a> to include people over 35. However, death rates from melanoma were unchanged compared to areas where skin exams were not offered. </p>
<p>The results of the German screening program did not provide strong confidence that annual widespread public screening of adults would reduce skin cancer deaths compared with current practices. However, the task force did conclude, based on numerous studies involving millions of patients, that detecting melanoma at early stages when tumors are less invasive <a href="https://doi.org/10.1001/jama.2023.3262">improved patient survival</a>. </p>
<h2>When should you get a skin exam?</h2>
<p>The American Academy of Dermatology, the <a href="https://www.skincancer.org/early-detection/self-exams/">Skin Cancer Foundation</a> and the <a href="https://www.cdc.gov/cancer/skin/basic_info/screening.htm">CDC recommend</a> <a href="https://www.aad.org/news/aad-statement-uspstf-cancer-screeening">monthly self-checks</a>. This requires familiarity with your skin or that of your family members. Luckily, there are many online guides on detecting suspicious skin lesions. </p>
<p>Whenever you have a concern about a spot on your skin, seek medical advice. Annual or more frequent exams are also <a href="https://www.aad.org/dw/dw-insights-and-inquiries/2019-archive/november/dwii-11-13-19-the-naked-truth-about-total-body-skin-examination-a-lesson-from-goldilocks-and-the-three-bears">recommended for high-risk groups</a>. This includes those who are older or susceptible to getting skin cancers, skin cancer survivors and immunocompromised people like organ transplant recipients. </p>
<p>Between 8% to 30% of the U.S. population <a href="https://doi.org/10.1016/j.jaad.2008.03.013">gets an annual skin exam</a>, but the numbers are imprecise because screening rates have not been well studied. Access to screening may also be challenging for some people. In response, nonprofits like the <a href="https://www.aad.org/public/public-health/skin-cancer-screenings/find-a-screening">American Academy of Dermatology</a>, <a href="https://www.skincancer.org/early-detection/destination-healthy-skin/">the Skin Cancer Foundation</a> and <a href="https://www.thesunbus.org/">The Sun Bus</a> provide resources for free exams. However, these opportunities are often few and far between. </p>
<p>Based on internal unpublished data from The Sun Bus, our mobile clinic operating in the central and southern U.S., a significant number of individuals seeking free exams were primarily motivated by concerns about a skin lesion and the cost of visiting a dermatologist.</p>
<p><iframe id="X7MiE" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/X7MiE/8/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>Our data suggests that screening programs attract individuals who are proactive and health-conscious.</p>
<h2>How can you minimize the risk of skin cancer?</h2>
<p>Strategies that limit UV exposure will <a href="https://www.cdc.gov/cancer/skin/basic_info/sun-safety.htm">reduce skin cancer risk</a>. This includes avoiding sunburns by: </p>
<ul>
<li>Finding shade</li>
<li>Covering exposed skin</li>
<li>Using a hat and sunglasses</li>
<li>Using and reapplying sunscreen routinely</li>
</ul>
<p>A broad-spectrum sunscreen and lip balm with a Sun Protection Factor (SPF) of at least 30 when applied correctly will <a href="https://www.aad.org/public/everyday-care/sun-protection/shade-clothing-sunscreen/how-to-select-sunscreen">block 97% of ultraviolet rays</a>. Apply these products 15-20 minutes before heading out into the sun and reapply every two hours. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/L7dH-I2qLU8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Don’t wait until you’re in the sun to apply sunscreen.</span></figcaption>
</figure>
<p>UV light is most intense between the hours of 10 a.m. to 4 p.m. It is a good idea to pay attention to the UV index – a forecast by zip code that <a href="https://www.epa.gov/sunsafety/uv-index-1">projects risk of UV exposure</a> on a scale of 0 to 11. A UV index below 2 is the safest, whereas 11 represents extreme danger. </p>
<p>Ideally, clothing should be rated with an Ultraviolet Protection Factor (UPF) of 50. Wearing regular long-sleeved clothing and pants will also <a href="https://www.skincancer.org/skin-cancer-prevention/sun-protection/sun-protective-clothing/">provide some protection</a>. </p>
<p>These measures can keep your skin healthy into your golden years by reducing skin aging and cancer caused by ultraviolet light.</p><img src="https://counter.theconversation.com/content/209371/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Enrique Torchia received funding from American Cancer Society and Dermatology Foundation. </span></em></p><p class="fine-print"><em><span>Neil Box receives funding from the National Institutes of Health and the American Skin Association. He is affiliated with Caris Life Sciences and the Colorado Melanoma Foundation. </span></em></p><p class="fine-print"><em><span>Tamara Terzian received funding from National Institutes of Health, Dermatology Foundation, Skin Cancer Foundation, American Skin Association, American Cancer Society, Cancer League of Colorado, and Colorado Clinical Translational Sciences Institute. She is affiliated with the Colorado Melanoma Foundation and the University of Colorado. </span></em></p>Widespread screening for skin cancer may not be necessary, but it is important to understand the risks behind UV overexposure and to get checked early if you have concerns.Enrique Torchia, Assistant Research Professor of Dermatology, University of Colorado Anschutz Medical CampusNeil Box, Associate Clinical Professor of Dermatology and Epidemiology, University of Colorado Anschutz Medical CampusTamara Terzian, Assistant Professor of Dermatology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1992492023-05-01T12:09:46Z2023-05-01T12:09:46ZEvery cancer is unique – why different cancers require different treatments, and how evolution drives drug resistance<figure><img src="https://images.theconversation.com/files/522691/original/file-20230424-26-vnh6yd.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2048%2C1560&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Most tumors are made up of many different kinds of cancer cells, as shown in this pancreatic cancer sample from a mouse.</span> <span class="attribution"><a class="source" href="https://visualsonline.cancer.gov/details.cfm?imageid=10654">Ravikanth Maddipati/Abramson Cancer Center at the University of Pennsylvania via National Cancer Institute</a></span></figcaption></figure><p>Cancer is an evolutionary disease. The same forces that turned <a href="https://evolution.berkeley.edu/what-are-evograms/the-origin-of-birds/">dinosaurs into birds</a> turn normal cells into cancer: genetic mutations and traits that confer a survival advantage.</p>
<p><a href="https://www.nature.com/scitable/knowledge/library/evolution-is-change-in-the-inherited-traits-15164254/">Evolution in animals</a> is largely driven by mutations in the DNA of germ cells – the sperm and egg that fuse to form an embryo. These mutations may confer traits that differ from those of the offspring’s parents such as larger paws, sharper teeth or lighter hair color. If the change is beneficial, like a mutation that lightens the hair of a rabbit living in a snowy climate, the animal is better able to survive, mate and pass on its mutated gene to the next generation. Such changes accumulate over millions of years, eventually turning, for example, dinosaurs into bluebirds.</p>
<figure>
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<figcaption><span class="caption">Evolution is natural selection of particularly advantageous traits over time.</span></figcaption>
</figure>
<p>Cancer arises by these same evolutionary pressures, but at the level of individual cells within a person’s body. Instead of animals fighting for survival in a harsh environment, <a href="https://theconversation.com/microbes-in-your-food-can-help-or-hinder-your-bodys-defenses-against-cancer-how-diet-influences-the-conflict-between-cell-cooperators-and-cheaters-195810">cells compete for space and nutrients</a>. Because different organs are composed of different kinds of cells, cancers arising from different organs differ from one another in appearance and behavior and in how well they respond to treatment.</p>
<p>We are a team of <a href="https://cancer.psu.edu/researchers/individual/-/researcher/5B6500F63D6A38DBE0540010E056499A/monika-joshi-md-mrcp">oncologists</a>, <a href="https://scholar.google.com/citations?user=YEqQHkIAAAAJ&hl=en">pathologists</a> and <a href="https://cancer.psu.edu/researchers/individual/-/researcher/5F6E820FF5C14A2DE0540010E056499A/joshua-warrick-md">translational scientists</a> who work together to study how cancers evolve. We believe that understanding evolution is key to understanding how cancer arises and how to treat it. </p>
<h2>Timing is of the essence</h2>
<p>Human cells are normally in a constant state of death and renewal. Old cells die and are replaced by new ones. These phases of death and renewal are usually orderly, with cells cooperating in a complex process that provides them with proper nutrition and replaces them at a constant rate, maximizing the overall function of the organ they make up. </p>
<p>Mutations disrupt this orderly process. Changes to the cell’s DNA alter the proteins that comprise the cell’s structure and govern its behavior, sometimes in ways that lead it to duplicate itself faster than its neighbors, resist normal death signals and sequester nutrients for itself. </p>
<p>The <a href="https://theconversation.com/anti-cancer-car-t-therapy-reengineers-t-cells-to-kill-tumors-and-researchers-are-expanding-the-limited-types-of-cancer-it-can-target-196471">immune system attacks and kills</a> mutant cells in most cases. However, if one survives and duplicates itself many times over, it can form a tumor made of multiple mutant cells. These tumor cells continue to reproduce and mutate, evolving until the tumor ultimately gains the ability to spread throughout the body.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of precancerous pancreatic tissue in mice" src="https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=452&fit=crop&dpr=1 600w, https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=452&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=452&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=568&fit=crop&dpr=1 754w, https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=568&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/523034/original/file-20230426-20-yhvhbj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=568&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This microscopy image shows precancerous pancreatic tissue in mice.</span>
<span class="attribution"><a class="source" href="https://directorsblog.nih.gov/2017/06/15/snapshots-of-life-a-van-gogh-moment-for-pancreatic-cancer/">Nathan Krah, University of Utah</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>Cancer detected at the earliest stages of this evolution can be treated more effectively than cancer at more advanced stages. This observation underlies the effectiveness of <a href="http://dx.doi.org/10.5888/pcd19.220063">cancer screening programs</a> in reducing cancer rates. </p>
<p>For example, <a href="https://www.cancer.org/cancer/colon-rectal-cancer/about/what-is-colorectal-cancer.html">colon cancer</a> begins as a polyp, a small tumor on the interior surface of the colon that is harmless on its own but may eventually evolve and gain the ability to invade the colon wall and spread throughout the body. Precancerous polyps are easily removed during <a href="https://theconversation.com/colonoscopy-is-still-the-most-recommended-screening-for-colorectal-cancer-despite-conflicting-headlines-and-flawed-interpretations-of-a-new-study-192374">colonoscopy screenings</a>, preventing them from evolving to invasive colon cancer. </p>
<h2>Different cancers require different treatments</h2>
<p>In general, cancers from different organs look distinct from one another and contain different proteins. This leads to variations in how they behave.</p>
<p>Under the microscope, cancer looks like a distorted and disorganized version of the normal tissue from which it arose. Cancer cells tend to contain the same set of proteins as those in healthy organs, and likewise continue to perform many of the same functions. For example, prostate cancer contains large amounts of <a href="https://doi.org/10.5534%2Fwjmh.180040">androgen receptors</a>, proteins that bind to testosterone and drives cells to grow and survive. Androgen receptors both enable normal prostate function and drive growth of prostate cancer.</p>
<p>Tumors arising in a given organ also tend to have mutations in the same set of genes, even among different patients. For example, around <a href="https://doi.org/10.1016/j.cell.2015.05.044">half of patients with melanoma</a>, an aggressive type of skin cancer, have a mutation in the BRAF gene that enhances cell growth and survival. In contrast, BRAF mutations are <a href="https://doi.org/10.1038/nature13385">rare in lung cancer</a>. </p>
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<figcaption><span class="caption">Pathologists look at tissue samples under a microscope to identify cancer cells.</span></figcaption>
</figure>
<p>Cancers also differ in the number of mutations they contain, and this number is strongly associated with the organ from which they arise. The prevalence of mutations is also influenced by mutations in genes that control DNA repair. For example, <a href="https://doi.org/10.1016/j.cell.2014.09.050">thyroid cancers</a> typically have a low number of mutations while <a href="https://doi.org/10.1038/nature11252">colon cancers</a> have many mutations, a number that is increased dramatically in tumors that have lost genes involved in DNA repair.</p>
<p>Because of these substantial differences in proteins and mutations, tumors from different organs respond differently to treatment. For example, the majority of patients with <a href="https://doi.org/10.1001/jama.1960.03030100059013">testicular cancer</a> can be cured with traditional chemotherapy combined with surgery. However, thyroid cancer and melanoma respond minimally to chemotherapy and require different approaches. Radioactive iodine can only be used to treat <a href="https://www.cancer.org/cancer/thyroid-cancer/treating/radioactive-iodine.html">thyroid cancer</a> because only thyroid cells take up iodine as part of their usual function.</p>
<p>Tumors that contain a large number of mutations often respond well to immunotherapies that help the patient’s immune system attack cancer cells. This is because the immune system sees tumors with more mutations as more foreign and thus mounts a greater response against them. For example, <a href="https://doi.org/10.1056/nejmoa1910836">melanoma</a> and <a href="https://doi.org/10.1056/nejmoa1613683">bladder</a> and <a href="https://doi.org/10.1056/NEJMoa1606774">lung cancers</a> respond well to immunotherapy, particularly those that have lost DNA repair function. In contrast, <a href="https://doi.org/10.1038/d41586-022-02861-y">prostate cancer</a>, which often harbors a low number of mutations, has typically responded poorly to immunotherapies.</p>
<h2>Treatments can drive cancer evolution</h2>
<p>Treatment can also <a href="https://theconversation.com/cancers-are-in-an-evolutionary-battle-with-treatments-evolutionary-game-theory-could-tip-the-advantage-to-medicine-170175">push cancer to evolve further</a>, gaining advantageous mutations that help them survive and resist therapy. </p>
<p>For example, a subset of lung cancers is driven by mutation in a <a href="https://theconversation.com/a-new-way-to-organize-cancer-mutations-could-lead-to-better-treatment-matches-for-patients-168348">gene called EGFR</a>. These are treated with a group of drugs that block the protein the mutant EGFR gene encodes for, slowing the cancer’s growth. Lung cancers treated with these drugs often develop a new EGFR mutation <a href="https://doi.org/10.1073/pnas.0709662105">called T790M</a> that confers resistance to most EGFR inhibitors. However, researchers have <a href="https://doi.org/10.1056/nejmoa1713137">developed another drug</a> that inhibits proteins with T790M and other EGFR mutations more broadly, improving survival for patients with these types of lung cancers.</p>
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<figcaption><span class="caption">Cancer cells can adapt to treatments and become resistant to them.</span></figcaption>
</figure>
<p>Similarly, metastatic prostate cancer is often treated with drugs that block androgen receptors, because it depends on them for growth and survival. Over time, the tumors <a href="https://doi.org/10.1158/0008-5472.can-08-3605">evolve in response to these drugs</a> and develop mutations that change the androgen receptor, massively increase the amount of androgen receptor they produce or, in some cases, completely change their appearance and protein content so they no longer rely on androgen receptors to survive. In these instances, patients require different therapies to overcome resistance. </p>
<h2>Not an easy fight</h2>
<p>The fight against cancer is a fight against evolution, the fundamental process that has driven life on Earth since time immemorial. This is not an easy fight, but medicine has made tremendous progress. </p>
<p>Deaths from cancer in the U.S. have <a href="https://gis.cdc.gov/Cancer/USCS/#/Trends/1,2,1,1,1,value,23">declined since the early 1990s</a>. Much of this is attributable to cancer screening programs and recently developed, more effective drugs. The U.S. Food and Drug Administration approved <a href="https://doi.org/10.1001/jamanetworkopen.2021.38793">332 new drug treatments for cancer</a> between 2009 and 2020. More new drugs are on the way.</p><img src="https://counter.theconversation.com/content/199249/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joshua Warrick receives funding from The National Institutes of Health. </span></em></p><p class="fine-print"><em><span>David DeGraff receives funding from the National Institutes of Health, Congressionally Directed Medical Research Fund/Department of Defense, the American Cancer Society, the Bladder Cancer Advocacy Network, and Bristol Myers Squibb. </span></em></p><p class="fine-print"><em><span>Monika Joshi receives funding from NIH, AstraZeneca, BMS for research related work. She has received funding for research from Pfizer and Eisai in the past. She has received personal fees for advisory board from Seagen, Sanofi and Bayer in the past. </span></em></p>There is no one-size-fits-all approach to treating cancer. Understanding how cancer cells evolve could help researchers develop more effective drugs.Joshua Warrick, Associate Professor of Pathology, Penn StateDavid DeGraff, Associate Professor of Pathology, Penn StateMonika Joshi, Associate Professor of Hematology and Oncology, Penn StateLicensed 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>
<figure>
<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>
</figure>
<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/1957922023-01-09T13:18:31Z2023-01-09T13:18:31ZHow cancer cells move and metastasize is influenced by the fluids surrounding them – understanding how tumors migrate can help stop their spread<figure><img src="https://images.theconversation.com/files/502978/original/file-20230103-70338-2503wk.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2476%2C1209&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tumor cells traverse many different types of fluids as they travel through the body.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/spreading-cancer-cell-illustration-royalty-free-illustration/1407269122">Christoph Burgstedt/Science Photo Library via Getty Images</a></span></figcaption></figure><p><a href="https://doi.org/10.1016/C2020-0-03305-0">Cell migration</a>, or how cells move in the body, is essential to both normal body function and disease progression. Cell movement is what allows body parts to grow in the right place during early development, wounds to heal and tumors to become metastatic.</p>
<p>Over the last century, how researchers understood cell migration was limited to the effects of biochemical signals, or <a href="https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/7%3A_Microbial_Genetics/7.21%3A_Sensing_and_Signal_Transduction/7.21A%3A__Chemotaxis">chemotaxis</a>, that direct a cell to move from one place to another. For example, a type of immune cell called a neutrophil migrates toward areas in the body that have a <a href="https://doi.org/10.4049/jimmunol.155.3.1428">higher concentration of a protein called IL-8</a>, which increases during infection.</p>
<p>In the past two or three decades, however, scientists have started to recognize the importance of the <a href="https://www.mechanobio.info/">mechanical, or physical, factors</a> that play a role in cell migration. For example, human mammary epithelial cells – the cells lining the milk ducts in the breast – <a href="https://doi.org/10.1126/science.aaf7119">migrate toward areas of increasing stiffness</a> when placed on a surface with a stiffness gradient.</p>
<p>And now, instead of focusing on just the effect of the “solid” environment of cells, researchers are turning toward their “fluid” environment. As a <a href="https://scholar.google.com/citations?user=nKmJNpQAAAAJ&hl=en">theoretician</a> trained in applied mathematics, I use mathematical models to understand the physics behind cell biology. My colleagues <a href="https://scholar.google.com/citations?user=otbcd-EAAAAJ&hl=en">Sean X. Sun</a> and <a href="https://scholar.google.com/citations?user=sMrPz8sAAAAJ&hl=en">Konstantinos Konstantopoulos</a> and I were among the pioneering scientists who discovered how <a href="https://doi.org/10.1242/jcs.240341">water and hydraulic pressure</a> influence cell migration through theoretical models and lab experiments. In our recently published research, we found that human breast cancer cell migration is enhanced by the <a href="https://doi.org/10.1038/s41467-022-33683-1">flow</a> and <a href="https://doi.org/10.1038/s41586-022-05394-6">viscosity</a> of the fluids surrounding them, clarifying one of the factors influencing how tumors metastasize.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/FD-A0MhYc7Y?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Cells can move in different ways.</span></figcaption>
</figure>
<h2>How fluids affect cell migration</h2>
<p>Cells in the human body are constantly exposed to fluids of <a href="https://doi.org/10.1038/s41586-022-05394-6">different physical properties</a>. Water is one such fluid that can direct cell migration. For example, we found that <a href="https://doi.org/10.1038/s41467-022-33683-1">how water flows across the membranes</a> of breast cancer cells influences how they move and metastasize. This is because the amount of water traveling in and out of a cell causes it to shrink or swell, inducing movement by translocating different parts of the cell.</p>
<p>The viscosity, or thickness, of body fluids varies from organ to organ, and from health to disease, and this can also affect cell migration. For example, the fluid between cancer cells in tumors is more viscous than the fluid between normal cells in healthy tissues. When we compared how quickly breast cancer cells move in confined channels filled with fluid of normal viscosity versus fluid of high viscosity, we found that cells in high viscosity channels <a href="https://doi.org/10.1038/s41586-022-05394-6">counterintuitively sped up</a> by a significant 40%. This discovery was unexpected because the fundamental laws of physics tell us that inert particles should slow down in high viscosity fluids due to increased resistance.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Animation comparing two fluids with lower and higher viscosity." src="https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=463&fit=crop&dpr=1 600w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=463&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=463&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=582&fit=crop&dpr=1 754w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=582&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/502975/original/file-20230103-105030-c8xq8d.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=582&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The blue fluid on the left has a lower viscosity relative to the orange fluid on the right.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/File:Viscosities.gif">Synapticrelay/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>We wanted to figure out the mechanism behind this surprising result. So we identified what molecules were involved in this process, discovering a cascade of events that allow high viscosity environments to enhance cell motility. </p>
<p>We found that high viscosity fluids first promote the growth of protein filaments called actin, which open channels in the cell’s membrane and increase water intake. The cell expands from the water, activating another channel that takes in calcium ions. These calcium ions activate another type of protein filament called myosin that induces the cell to move. This cascade of events induces cells to change their structure and generate more force to overcome the resistance imposed by high viscosity fluid, meaning the cells aren’t inert at all.</p>
<p>We also discovered that cells retained “memory” after exposure to a high viscosity medium. This meant that if we put cells in a high viscosity medium for several days and then returned them to a normal viscosity medium, they would still move at a faster speed. How cells retain this memory is still an open question.</p>
<p>We then wondered whether our findings on viscous memory would remain true in animals, not just in Petri dishes. So we exposed human breast cancer cells to a high viscosity medium for six days, then placed them in a normal viscosity medium. We then injected the cells into chicken embryos and mice.</p>
<p>Our results were consistent: Cells pre-exposed to a high viscosity medium had an increased ability to leak into surrounding tissues and metastasize compared to cells that were not pre-exposed. This result demonstrates that the viscosity of the fluids in a cell’s surrounding environment is a mechanobiological cue that promotes cancer cells to metastasize.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/OcigJn8UJNQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Understanding how cells move could help elucidate how tumors metastasize.</span></figcaption>
</figure>
<h2>Implications for cancer treatment</h2>
<p>Cancer patients usually don’t die from the original source of the tumor, but from its <a href="https://doi.org/10.1002%2Fcam4.2474">spread to other parts of the body</a>.</p>
<p>When cancer cells travel through the body, they move into spaces that will have varying fluid viscosity. Understanding how fluid viscosity affects the movement of tumor cells could help researchers figure out ways to better treat and detect cancer before it metastasizes. </p>
<p>The next step is to build imaging and analysis techniques to precisely examine how cells from various types of lab animals respond to changes in fluid viscosity. Identifying the molecules that regulate how cells respond to changes in viscosity could help researchers identify potential drug targets to reduce the spread of cancer.</p><img src="https://counter.theconversation.com/content/195792/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yizeng Li receives funding from National Science Foundation.</span></em></p>Counterintuitively, cells move faster in thicker fluids. New research on breast cancer cells explains why, and reveals the role that fluid viscosity plays in metastasis.Yizeng Li, Assistant Professor of Biomedical Engineering, Binghamton University, State University of New YorkLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1562792021-06-27T12:35:37Z2021-06-27T12:35:37ZHow tiny gold particles injected into tumours could improve radiation treatment for cancer<figure><img src="https://images.theconversation.com/files/406256/original/file-20210614-107575-sauotc.jpg?ixlib=rb-1.1.0&rect=212%2C139%2C4448%2C3399&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The limiting factor in cancer radiotherapy is that doses high enough to try to cure tumours also damage surrounding normal tissues.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Cancer is the second leading cause of death globally. In 2018, there were 18.1 million new cases and <a href="https://www.cancer.gov/about-cancer/understanding/statistics">9.5 million cancer-related deaths worldwide</a>. By 2040, the number of new cancer cases per year is expected to rise to 29.5 million and the number of cancer-related deaths to 16.4 million. </p>
<p>Approximately <a href="https://doi.org/10.1016/j.radonc.2014.03.024">50 per cent of all cancer patients can benefit from radiotherapy</a> in the management of their disease. About half of those patients are <a href="http://hdl.handle.net/10986/22552">diagnosed early enough that their cancer may be curable</a>. For many cancers including breast, prostate, cervix, head and neck, lung and brain cancers, curative treatment includes radiation therapy. However, because radiotherapy destroys healthy cells as well as tumour cells, doses are limited.</p>
<p><a href="https://www.cancer.ca/en/cancer-information/diagnosis-and-treatment/radiation-therapy/?region=on">Radiotherapy</a>, also called radiation therapy, is used alone to treat cancer or with other treatment options such as chemotherapy and surgery. It may also be used to shrink the tumour before surgery. In radiotherapy, tumour cells — which divide much faster than other surrounding healthy cells — are destroyed by damaging their DNA. </p>
<h2>Side-effects limit radiation dose</h2>
<p>The limiting factor in radiotherapy is that doses high enough to try to cure high-risk (locally advanced) non-metastatic tumours also damage surrounding normal tissues. Currently, we are at the limit of radiotherapy dose that can be given to patients. To further improve survival, there is a need for new methods that enhance radiation effectiveness while reducing side-effects.</p>
<p>One way to accomplish this is by making tumour cells more sensitive to radiation, so those cells are more easily damaged by radiation therapy. Using <a href="https://doi.org/10.1667/rr1984.1">gold nanoparticles as radiosensitizers</a> has shown promising results. These gold nanoparticles can be introduced intravenously to accumulate in the tumour by exploiting the faulty walls of the tumour’s blood vessels, <a href="https://doi.org/10.3390/cancers10030084">which tend to be leaky because of fast growth</a>. </p>
<p>Gold nanoparticles interact with X-ray photons used in radiation treatment which produces electrons, which then interact with water molecules to produce free radicals. These free-radicals can damage cells, lowering the survival of those cells. </p>
<p>Understanding the complex biological system present in and around the tumour is essential for optimizing the use of the radiosensitizing GNPs, as <a href="https://doi.org/10.1016/j.ijrobp.2015.09.032">outlined by a consortium of labs</a>, including our own nanoscience and technology development laboratory at University of Victoria. </p>
<h2>Targeting interactions inside the tumour</h2>
<p>In this work, we discuss the importance of looking into which cellular components within the tumour microenvironment take up the gold nanoparticles and become radiosensitized. We are particularly interested in cells called activated fibroblasts, which are associated with wound healing and have anti-tumourogenic properties, meaning they help fight tumour growth. </p>
<p>However, activated fibroblasts can be recruited by the tumour cells, and become cancer-associated fibroblasts (CAFs). Instead of anti-tumourigenic properties, CAFs promote the proliferation and metastasis of tumours. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of the types of cells found in the microenvironment of a tumour." src="https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=486&fit=crop&dpr=1 600w, https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=486&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=486&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=610&fit=crop&dpr=1 754w, https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=610&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/387339/original/file-20210302-15-4fg45x.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=610&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Incorporating gold nanoparticles into current radiation treatment protocols had three goals: to enhance killing of tumour cells, to target CAFs and to protect fibroblasts.</span>
<span class="attribution"><span class="source">Reproduced with permission (Bromma et al.(2020), Sci Reports, 10, 2181).</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>The function of CAFs supports the idea that tumours are “wounds that do not heal,” and targeting CAFs may prove beneficial towards improved cancer treatment outcomes. </p>
<p>As illustrated in the image above, our research on incorporating gold nanoparticles into current radiation treatment protocols had three goals: to enhance killing of tumour cells, to target CAFs and to protect fibroblasts. </p>
<p>For radiosensitizing to be effective in improving radiation treatment, the cells targeted by the treatment (the ones associated with cancer growth) need to have high uptake of the radiosensitizing particles, while the beneficial cells need to have a low uptake. This makes the targeted cells are more easily destroyed by radiation therapy at doses that patients can tolerate. </p>
<p>These results using 3D tumours grown in the lab are very encouraging. The CAFs had the largest uptake of the gold nanoparticles per cell, with almost triple that of cancer cells, while fibroblasts had a relatively small number. This also translated to a larger increase in DNA damage in the CAFs compared to the other cell types, reducing the activity of the CAFs and slowing tumour growth. </p>
<p>This difference in DNA damage due to selective targeting of cancer-associated cells over normal cells may allow gold nanoparticles to be an effective tool in future cancer radiation therapy, helping to minimize damage to normal tissue while improving local radiation therapy dose to the tumour.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Gold nanoparticles in red against a green background of the tumour, with a bar graph showing uptake of the nanoparticles." src="https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/387338/original/file-20210302-17-fx2m8l.png?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"></a>
<figcaption>
<span class="caption">Accumulation of gold nanoparticles (red) in the tumour environment.</span>
<span class="attribution"><span class="source">Reproduced with permission (Bromma et al.(2020), Sci Reports, 10, 2181).</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>This study showcases that using gold nanoparticles as a radiosensitizer allows more damage to be propagated to the CAFs, an element that has shown to be largely <a href="https://doi.org/10.1038/s41598-020-68994-0">influential to the progression of cancer</a>. We believe that this work will be a building block towards a more effective treatment regime in the near future. Building a model that can accurately represent the different interactions taking place inside the tumour’s microenvironment is essential to improving treatment results for patients.</p><img src="https://counter.theconversation.com/content/156279/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Devika Basnagge Chithrani receives funding from Natural Sciences and Engineering Research Council, Canada Foundation for innovation, British Columbia Knowledge Development Fund and University of Victoria.. </span></em></p>Higher doses of radiotherapy for cancer treatment destroy more healthy tissue as well as more tumour cells. Gold nanoparticles sensitize tumours to radiation, making treatment more effective.Devika Basnagge Chithrani, Associate professor, Physics and Astronomy/Medical physics, University of VictoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1144952019-05-03T10:43:42Z2019-05-03T10:43:42ZPlatelets: The chameleons of cancer biology<figure><img src="https://images.theconversation.com/files/272278/original/file-20190502-103082-1li7vsn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Activated platelets (purple) on their way to heal a wound.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-medically-accurate-illustration-active-1343108396?src=1hKNrj9qhV9M8ikZLW1h-A-1-20">Sebastian Kaulitzki/Shutterstock.com</a></span></figcaption></figure><p>Have you ever been in a classroom and wondered to yourself whether the information being presented could be wrong? </p>
<p>During graduate school, I audited a medical school class in which the professor remarked that at some point in the students’ medical training, a fact would be presented that later may be shown to be incorrect. </p>
<p>New discoveries are continuously upending our most fundamentally held dogmas. One area currently being reexamined is the complicated interactions between the components of blood with your body. Don’t worry; just like your high school textbook says, red blood cells still bring oxygen from the lungs to rest of the body, and white blood cells are still protecting your body from foreign invaders. However, the more subtle roles of blood, especially in diseases like cancer, are not fully understood.</p>
<p>I am a cell and molecular biologist, and my background in research began with studying changes within cells that <a href="https://doi.org/10.1038/oncsis.2016.36">cause</a> <a href="https://doi.org/10.21873/anticanres.11074">cancer</a>. My interest in cancer eventually led me to explore how tumors are supplied with adequate nutrition. One blood component continued to arise in literature, displaying an interesting and dynamic role after a person develops cancer: platelets. </p>
<h2>Platelets and cancer</h2>
<p>Platelets are the component of blood that springs into action when you get a paper cut or scrape your knee. The signals governing the recognition of a wound, and how to address healing, are quite complicated. However, under normal physiological conditions, these signals mediate a process called platelet activation, which results in healing the wound by closing broken blood vessels. </p>
<p>In addition to this well-known role, scientists have uncovered many other functions of platelets. In fact, an association between higher numbers of platelets and the progression of cancer has been recognized for nearly five <a href="https://doi.org/10.1002/ijc.2910110322">decades</a>. Platelet numbers are elevated in cancer patients, and studies have shown that platelet-mediated blood clots are associated with tumor cell <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665369/">metastasis</a>.</p>
<p>That suggests that platelets may be linked to the spread of cancer to other parts of the body. But that may not be the only thing the platelets do for cancer.</p>
<p>Platelets, along with other cell types, release microparticles which respond to a variety of stimuli, including those which mediate platelet <a href="https://doi.org/10.1111/j.1365-2141.1967.tb08741.x">activation</a> for wound healing. </p>
<p>While the mechanisms of microparticles are not completely understood, several <a href="http://doi.org/10.1371/journal.pone.0050746">studies</a> have demonstrated they contain molecules that modulate which genes are turned on and off. Altering gene activity ultimately affects the production or turnover of proteins, which can cause a multitude of changes that affect health. Interestingly, microparticles contain molecules that have been shown to alter gene expression, and are associated with cancer progression.</p>
<p>That brings up an interesting question: Is it possible that platelets and the microparticles they release upon activation could also modulate cancer progression?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=524&fit=crop&dpr=1 600w, https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=524&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=524&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=659&fit=crop&dpr=1 754w, https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=659&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/272032/original/file-20190501-113830-9e06ae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=659&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Platelets heal broken blood vessels.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/platelets-thrombocyte-activation-fibrin-blood-vessel-1014485002?src=CiRk4tbLuy1nvQ4IZstkMw-1-15">VectorMine/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Do platelets drive cancer?</h2>
<p>My colleagues and I sought to address this, beginning with perhaps the most important question: whether platelet-derived microparticles were detectable in patient cancer tissue. Indeed, using a high-resolution microscope we observed microparticles in <a href="https://doi.org/10.1182/blood-2016-11-751099">cancers from many tissue types</a>. </p>
<p>Importantly, we did not see microparticles in normal tissue from the same patient, indicating they were specifically targeting cancer cells. </p>
<p>This was a particularly interesting observation, because until then, these vesicle-like structures were hypothesized to affect only other cells within the blood vessel, and not target any other surrounding cells. Our team demonstrated that platelet-derived microparticles specifically target tumors. </p>
<p>Moreover, those targeted cells absorbed the gene-regulating molecules within the microparticles. However, contrary to our original hypothesis, we observed that microparticles inhibited solid tumor growth. This finding showed that platelets may not be so easy to pick on as only a bad guy in cancer progression. </p>
<h2>Rethinking the role of platelets</h2>
<p>New information has enabled researchers like myself to reevaluate our understanding of the role of platelets in cancer. Until recently, relatively few studies have observed a protective role of <a href="https://doi.org/10.1002/ijc.29847">platelets in cancer</a>. </p>
<p>While there is substantial evidence linking intact platelets to promoting cancer, the dual pro- and anti-cancerous roles of platelets raise some fascinating questions about both intact platelets and the microparticles that they release. </p>
<p>In this way, it is tempting to consider platelets as so-called chameleons within the realm of cancer biology. The intact platelets appear to promote cancer progression, but the microparticles do the opposite, creating a natural check-and-balance system.</p>
<p>Further, the so-called leaky nature of tumor blood vessels has been posited as a likely reason for microparticles to have access to cancerous, but not normal, <a href="https://doi.org/10.3389/fcvm.2018.00013">tissue</a>. It is enticing to consider that someday, with a bit more characterization regarding the cargo being transferred, scientists could utilize the body’s natural delivery of extracellular vesicles, like these microparticles, as a therapeutic resource.</p><img src="https://counter.theconversation.com/content/114495/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>James Michael received funding from NHLBI, grant ID F32 HL139035. </span></em></p>Platelets heal wounds. But they also seem to play a paradoxical role in both promoting and inhibiting the growth of solid tumors.James Michael, Lecturer of Biochemistry, Thomas Jefferson UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/949562018-04-27T10:12:52Z2018-04-27T10:12:52ZWhy cancer cells go to sleep<figure><img src="https://images.theconversation.com/files/215412/original/file-20180418-163978-ajs5uy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Prostate cancer cell, viewed with a scanning electron microscope.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/202719580?src=3_jdSrXklM_AUW9qJtKSZQ-1-7&size=medium_jpg">royaltystockphoto.com/Shutterstock.com</a></span></figcaption></figure><p>Cancer has always been thought of as something that grows rapidly and uncontrollably, but this view may be wrong. New evidence suggests that cancer alternatively uses the “accelerator” and the “brake” in order to survive. </p>
<p>If you plot the growth of prostate cancer tumour progression over years, you get a graph that looks something like this:</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/215607/original/file-20180419-163991-18uio4s.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/215607/original/file-20180419-163991-18uio4s.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=311&fit=crop&dpr=1 600w, https://images.theconversation.com/files/215607/original/file-20180419-163991-18uio4s.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=311&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/215607/original/file-20180419-163991-18uio4s.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=311&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/215607/original/file-20180419-163991-18uio4s.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=391&fit=crop&dpr=1 754w, https://images.theconversation.com/files/215607/original/file-20180419-163991-18uio4s.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=391&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/215607/original/file-20180419-163991-18uio4s.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=391&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Figure 1. An example of prostate cancer progression.</span>
<span class="attribution"><span class="source">Modified from: http://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(15)00034-9</span></span>
</figcaption>
</figure>
<p>The graph shows that prostate cancer cells alternate periods of rapid growth with periods of dormancy. In the above example, the tumour will grow to the point where it starts to produce symptoms and the patient seeks treatment – which usually involves cutting the tumour out.</p>
<p>Surgery is often effective but, for some unfortunate patients, their cancer will return. At this point it is often treated with hormone therapy and chemotherapy. But even these treatments don’t always spell the end of the cancer. For some patients, the cancer will recur after a period of dormancy.</p>
<p>During the periods of dormancy, which could last several years, the patient will often have no symptoms and the tumour will be undetectable using the usual diagnostic tools. Until recently, we knew very little about these periods. However, research conducted by my group and by other scientists suggests that cancer dormancy is a crucial time for tumour progression. </p>
<h2>Dangers of cancer dormancy</h2>
<p>To understand why dormancy is useful to cancer cells, we need to examine the factors that can stop tumour progression. Cancer cells face three main challenges to their survival and growth. First, they need to <a href="http://www.cancerresearchuk.org/about-cancer/what-is-cancer/body-systems-and-cancer/the-immune-system-and-cancer">deceive the immune system</a>, which is able to eliminate most tumours. Second, they need to survive anti-cancer therapies, and, third, they need to invade distant organs and generate metastases.</p>
<p>Cancer dormancy is <a href="http://www.springer.com/gb/book/9783319592404">essential</a> to meet all these challenges. During the periods of dormancy, cancer cells reshape their genetic make-up and get ready for the next stage of progression. Without dormancy, cancer cells would not be able to survive in a new environment or become resistant to the attacks of the immune system. So it is important to learn how to detect dormant cancer cells, and how to kill them.</p>
<p>Detecting dormant cells is not easy, though. Dormant tumours are often small and don’t produce symptoms, so patients are often unaware of them and conventional diagnostic tools are unable to “see” them. Also, dormant cancer cells are often in slow-metabolism mode, like hibernating animals. So even some sophisticated diagnostic techniques, such as PET scans, often overlook dormant tumours. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/215597/original/file-20180419-163966-pglhgs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/215597/original/file-20180419-163966-pglhgs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=414&fit=crop&dpr=1 600w, https://images.theconversation.com/files/215597/original/file-20180419-163966-pglhgs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=414&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/215597/original/file-20180419-163966-pglhgs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=414&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/215597/original/file-20180419-163966-pglhgs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=520&fit=crop&dpr=1 754w, https://images.theconversation.com/files/215597/original/file-20180419-163966-pglhgs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=520&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/215597/original/file-20180419-163966-pglhgs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=520&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dormant cancer cells share some similarities with hibernating animals.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/788986813?src=mZXXsesHXItQnQL56YPUYg-1-0&size=medium_jpg">Breck P. Kent/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Detection and treatment</h2>
<p>So how do we detect these dangerous sleeping cells? Fortunately, new studies are shedding light on the characteristics of dormant cancer cells. For example, our research, in collaboration with the <a href="http://www.bccrc.ca/dept/et/personnel%20-%20content/principal-investigators/dr.-yuzhuo-wang">BC Cancer Agency</a> in Canada, has looked at the RNA produced by dormant and proliferating cancer cells. RNA is a very important molecule that carries the genetic information from DNA (the blueprint) to proteins (the cells’ workhorses). </p>
<p>We have shown that some small RNAs are <a href="http://oro.open.ac.uk/50028/1/41598_2017_Article_3731.pdf">specifically expressed</a> by dormant cancer cells. Since these RNAs can be measured in urine and blood samples, we, and others, are trying to develop new diagnostic tools to detect these molecules. If we are successful, we will be able to develop blood or urine-based diagnostic kits that will help doctors identify dormant tumours before they become too big to effectively treat.</p>
<p>Once dormant cancer cells have been identified, they need to be eliminated. Unfortunately, since these cancer cells are metabolically inactive, they are less likely to be killed by conventional chemotherapy, so targeting them is difficult. Difficult, but hopefully not impossible. </p>
<p>A number of new studies show that dormant cells might have weak spots. For example, experiments have shown that some <a href="https://www.statnews.com/2018/04/11/cancer-tumor-cells-mice-metastasis-nsaid/">nonsteroidal anti-inflammatory drugs</a> could stop dormant cancer cells that generate metastasis from “waking up”. If these results are confirmed by clinical trials, we will soon be able to offer the patients treatments that specifically target dormant cancer cells.</p><img src="https://counter.theconversation.com/content/94956/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Francesco Crea has received funding from Cancer Research UK, ASCO, Santander, Prostate Cancer Foundation BC and the Michael Smith Foundation, . He is affiliated with the European Association for Cancer Research. </span></em></p>Cancer doesn’t just grow uncontrollably. It has a smarter strategy than that.Francesco Crea, Lecturer in Life Sciences, The Open UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/880482017-12-05T10:09:18Z2017-12-05T10:09:18ZIt’s time to rethink how we do cancer research<figure><img src="https://images.theconversation.com/files/197343/original/file-20171201-17366-5vtw8e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Apple's Eyes Studio/Shutterstock.com</span></span></figcaption></figure><p>“<a href="https://www.theguardian.com/commentisfree/2017/oct/05/cancer-patients-survival-miracle-cures-medical-research">A devastating failure of medical research</a>.” This was the response of one cancer survivor on hearing the news that <a href="http://www.bmj.com/content/359/bmj.j4530?ijkey=09b39d8e242c6b801a1c36807974896d933fd707&keytype2=tf_ipsecsha">over half</a> of European Medical Agency-approved cancer treatments between 2009 and 2013 had no evidence of impact on quality of life or overall survival. As a cancer researcher, my goal above all is to improve patients’ lives – the fact we are failing at that struck me deeply.</p>
<p>Understandably, some people living with cancer are angry, feel betrayed, and are questioning why we do the research we do. Have cancer researchers lost sight of what is important in patient care? </p>
<p>Most anti-cancer treatments are first trialled in patients where cancer has already spread beyond a curable reach (the metastatic stage). This is because we feel we can’t offer an unproven treatment when others are available. Drug trials then tend to move to an earlier stage – take the example of <a href="http://news.bbc.co.uk/1/hi/health/5058952.stm">Herceptin</a>, which was developed to combat metastatic disease, but had such a huge impact it quickly moved to the curative early treatment stage. </p>
<p>This approach may seem to make sense, but right now, there is a bottleneck of treatments that have only limited benefit in delaying further spread of cancer in the metastatic stage. For many of these treatments, it is unlikely they will move to the curative stage as the benefits just don’t seem good enough. </p>
<p>Given all this, I think we need drastically to rethink our approach. </p>
<h2>Patients first</h2>
<p>We need to listen to what matters to patients. It is <a href="https://www.openaccessgovernment.org/highlighting-basic-research-cancer-treatment/22390/">often argued</a> that research needs space for blue sky thinking, the freedom to explore pathways and structures. But is there still room for that when we are confronted with the realities of increasing cancer rates, poor quality of life, with a 40-year-old with metastatic pancreatic cancer, for whom survival rates have <a href="https://www.sciencedaily.com/releases/2014/08/140807105106.htm">not improved</a> in the past four decades?</p>
<p>It is over ten years since the landmark <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360101/">MacMillan Listening Study</a> published its findings from in-depth consultations with groups of cancer patients and carers about their experiences. At that time, as now, the highest priority for patients was learning to live well with cancer. New treatments lagged significantly behind, coming in at number seven in patient’s priorities for cancer research. Yet fundraising campaigns still often focus on “finding a cure”. The emotional grab of a potential new anti-cancer treatment is seized on by reporters whereas the subtler improvements in quality of life are not. This means that funding for cancer research is skewed towards finding new treatments.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/197572/original/file-20171204-4062-ndkttn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Patients need to be prioritised over research questions.</span>
<span class="attribution"><span class="source">Alexander Raths/Shutterstock.com</span></span>
</figcaption>
</figure>
<p>We know early detection of cancer is key to improving survival ─ research in this area is not easy and doesn’t move quickly. Only this year has exclusive funding from Cancer Research UK <a href="http://www.cancerresearchuk.org/funding-for-reseachers/research-features/2017-06-19-new-funding-for-early-detection-research">been set aside</a> for early detection. But we need to encourage more research in this area. </p>
<p>Another area of chronic underfunding is <a href="http://stm.sciencemag.org/content/5/196/196cm6.full">biomarker research</a> – many currently available treatments don’t benefit everyone, but we don’t know how to select which individuals they do benefit. Making our existing treatments better rather than continuing to chase new treatments is often neglected.</p>
<p>We have seen some improvements in this area in recent years, particularly in the inclusion of patients and carers in developing cancer research. In my experience, these are motivated, caring individuals who are, more often than not, supportive of the research we do. But researchers need to be wary that we do not simply invite those whose voices we wish to hear – we must also include those who dissent with our views and challenge our research.</p>
<h2>Clinical trials</h2>
<p>Clinical trials tend to be designed around what we as researchers want to know, not always what patients need. I remember an impassioned plea for improved innovative trials from a woman who had lost her husband to melanoma. Even though they didn’t end up receiving the standard chemotherapy treatment (the control arm), her fear of her husband being selected for standard chemotherapy was so overwhelming it was now all she could remember. Can we focus our energy on making our trials better, switch up the design?</p>
<p>And of course, the trials are often funded by pharmaceutical companies, who want to show their drug in the best light. Today, many of our patients are too old for clinical trials, with the result that trials don’t necessarily reflect the real world of clinical treatment. In addition, several pharmaceutical companies can chase the same target, each hoping theirs is “the best”. This can saturate the market with “me too” drugs and stifle real innovation. The pharmaceutical industry has an important role to play, and they often play it well, of driving new treatments forward. But their need to keep an eye on the bottom line can be a distraction from the patient-centred research we need.</p>
<p>So what are some ways forward? We need a shift in research, away from a drug-focused approach to a more patient-focused approach, enshrining quality of life as a key outcome in clinical trials, ensuring we don’t accept inferior measurements of clinical benefit to approve a treatment. Most importantly, we need to value patients and carers as key partners in the progression of research. </p>
<p>By turning to those experiencing cancer treatment for the next big research questions and listening carefully to their answers, we can ensure those funding and performing research don’t get lost in a science maze, but have a clear view of the patient with every experiment.</p><img src="https://counter.theconversation.com/content/88048/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eileen Parkes receives funding from the Academy of Medical Sciences.</span></em></p>We need to ensure cancer research addresses what matters most.Eileen Parkes, Academic Clinical Lecturer, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/556192016-03-03T05:39:35Z2016-03-03T05:39:35ZChronic stress effects help cancer spread, researchers find<figure><img src="https://images.theconversation.com/files/113635/original/image-20160302-25879-17wt03c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Prolonged periods of stress can aid in the spread of cancer.</span> <span class="attribution"><span class="source">from shutterstock.com</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Chronic stress accelerates cancer growth in mice, according to a <a href="http://www.nature.com/ncomms/2016/160301/ncomms10634/full/ncomms10634.html">paper published in Nature Communications</a> this week. The finding points to potential treatment targets to slow the progression of cancer to other organs.</p>
<p>The paper revealed findings from several studies, mostly on mice, conducted by a team of researchers from Monash University.</p>
<p>Chronic stress refers to prolonged, repeated exposure to stressful situations, such as caring for a sick relative for a long period of time. To mimic the way people feel under significant stress, researchers restrained mice with breast cancer tumours, to make them feel like they couldn’t cope with their circumstances.</p>
<p>Over time, the mice developed an increase in the number and size of of their lymphatic vessels – a network of vessels that transports fluid around the body. This enhanced the spread of cancer cells to new sites, a process called cancer progression or metastasis.</p>
<p>By blocking the activity of proteins that detect stress, or those that enhance the formation of lymphatic vessels, researchers found they could reduce the spread of cancer cells in the mice. </p>
<h2>What stress does to the body</h2>
<p>The research focused on metastasis of breast cancer to other parts of the body, building on previous findings that neurological stress hinders our defence against disease.</p>
<p>Previous findings <a href="http://www.nature.com/nrclinonc/journal/v5/n8/full/ncponc1134.html">from human studies</a> have shown poorer cancer survival in people exposed to stressful life experiences and those more prone to stress. </p>
<p>Another <a href="http://onlinelibrary.wiley.com/doi/10.1002/cncr.23969/abstract;jsessionid=5F1E795CA48D6B71FC0A85B45799D348.f04t03">clinical trial</a> showed better survival rates for breast cancer patients in remission who participated in a 12-month intervention with strategies to reduce stress, improve mood and alter health behaviours.</p>
<p>Everyday stressful experiences pose a threat to the body’s natural balance. This is because stress activates the <a href="https://www.sciencedaily.com/terms/sympathetic_nervous_system.htm">sympathetic nervous system (SNS)</a>, which is responsible for what we know as the fight or flight response. </p>
<p>Under stress, the SNS releases higher levels of neurotransmitters. These hormones, such as epinephrine, signal to other cells to activate physiological flight or flight responses, such as a faster heart rate. This is important during times of threat because it makes us more alert and increases physiological functions needed for rapid reactions.</p>
<p>But as shown in the Nature Communications study, chronic periods of stress can lead to changes in the lymphatic system. These include an increase in the number of vessels in the tumours as well as the size of these vessels. These changes are associated with the spread of cancer cells to lymph nodes and distant organs, such as the lung. </p>
<p>Clinically, we know that when cancer cells have spread through blood vessels into the lymph vessels, that’s an important indicator of poorer prognosis. Preventing this could improve survival rates.</p>
<h2>It’s not so simple</h2>
<p>The latest findings have obvious treatment implications, which include using drugs to block stress responses that lead to changes in lymphatic vessels. But blocking any part of a natural pathway can promote a cascade of negative effects.</p>
<p>The study reported that a number of patients on drugs often used to treat anxiety and high blood pressure (beta blockers that block the actions of adrenaline) were less likely to have secondary cancer that had spread from its primary site. </p>
<p>This is good news, but more work is needed before such interventions can be further tested. </p>
<p>This is because the lymphatic system is important in our immune response and manipulating any of its mechanisms could carry potential harms. These include limiting the immune system’s ability to respond to the cancer in the first place. </p>
<p>It could also increase the risk of lymphedema – swelling in one or more extremities – that results from impaired flow of the lymphatic system.</p>
<p>Although the authors did show supportive data from human clinical subjects, the bulk of the work was done in mouse models. Results from mice experiments don’t always translate to human systems, so further clinical testing is an essential step in translating these findings.</p>
<p>Overall, though, the study points the way to potentially helping prevent cancer spreading so far from the original site that it’s too hard to treat.</p><img src="https://counter.theconversation.com/content/55619/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Chronic stress accelerates cancer growth in mice, according to a new study, pointing to potential treatment targets to slow the progression of cancer to other organs.Rik Thompson, Professor of Breast Cancer Research, Institute of Health and Biomedical Innovation and School of Biomedical Sciences,, Queensland University of TechnologySandra Hayes, Professor, School of Public Health and Social Work, Queensland University of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/466242015-08-26T19:45:14Z2015-08-26T19:45:14ZTreating ‘stage 0’ breast cancer doesn’t always save women’s lives so should we screen for it?<figure><img src="https://images.theconversation.com/files/92976/original/image-20150826-32480-j0rt1g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Women with DCIS or stage 0 breast cancer have the same chance of dying from breast cancer as the rest of the population – 3.3%.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-243901117/stock-photo-woman-in-s-about-to-undergoing-a-mammography-test.html?src=I7c8Kyu33z1Lv4w5zQVYOA-1-19">CristinaMuraca/Shutterstock</a></span></figcaption></figure><p>We’re told that “prevention is better than cure”; that finding symptoms of disease early will prevent the more serious consequences of that disease, particularly for cancer. </p>
<p>Women largely understand that a regular screening mammogram may decrease their chance of dying from the disease by allowing earlier detection and therefore less aggressive treatments. This is <a href="http://cancerscreening.gov.au/internet/screening/publishing.nsf/Content/programme-evaluation">largely true</a>: for every 1,000 women screened over a 25 year period, nine will not die from breast cancer because of that screening. But it does not give the entire picture.</p>
<p>For a minority of women diagnosed with the “pre-cancerous” lesion ductal carcinoma in situ, or DCIS, treatment doesn’t reduce their chance of getting or dying from breast cancer.</p>
<p>DCIS consists of abnormal cells in the breast ducts that rarely cause any symptom but are detectable on mammogram, often calcium deposits in the breast. This is also known as “stage 0” breast cancer. </p>
<p>Many of these indolent lesions are unlikely to ever cause a problem in a woman’s lifetime. So finding one can be said to be “over-diagnosis”. This detection will result in “overtreatment”, with surgery (lumpectomy or mastectomy, where the lump or breast is removed) and perhaps radiotherapy. </p>
<p>A <a href="http://canceraustralia.gov.au/publications-and-resources/position-statements/overdiagnosis-mammographic-screening">recent Australian analysis</a> concedes it is hard to put a definite figure on this, but it around eight women in every 100 screened over 25 years may have one of these “over-diagnosed” and “over-treated” lesions.</p>
<p>The real problem is that we currently have little ability to predict which of these DCIS lesions will either progress into an invasive cancer or predict the development of a future invasive cancer, with the potential to spread and impact on a woman’s life.</p>
<p>A study released last week in <a href="http://oncology.jamanetwork.com/article.aspx?articleid=2427491">JAMA Oncology</a> adds further data to this debate, but perhaps leads to more questions than answers. This study is a detailed examination of a huge North American registry database of outcomes of 100,000 women diagnosed with DCIS between 1988 and 2011 were studied. </p>
<p>The authors show that, overall, women diagnosed with DCIS have the same chance of dying of breast cancer than women with no breast problems: 3.3% after 20 years of follow up. </p>
<p>However, there were some important exceptions. Very young women (under 35) diagnosed with DCIS, women of African American ethnicity, and those with the more aggressive types of DCIS (larger, high-grade and non-hormone-dependent) had a higher risk of dying of breast cancer. </p>
<p>The researchers found treating DCIS did not save lives. Having a more radical surgery – mastectomy rather than lumpectomy – or adding radiotherapy to a lumpectomy overall did not decrease the chance of ultimately dying of breast cancer.</p>
<p>Interestingly, having a mastectomy or radiotherapy lowered the chance of getting an invasive cancer in the treated breast yet did not alter the chance of dying of breast cancer. This suggests that some DCIS lesions do have the ability to spread.</p>
<p>What can we conclude from this study? Well, it seems to confirm that there are at least two types of DCIS – and the more aggressive one <em>does</em> need to be treated.</p>
<p>But the majority of women with DCIS will not go on to get invasive cancer. So perhaps we need to consider DCIS more as a warning sign of potential future cancer risk. This opens the way for new research into less aggressive treatments for these types of DCIS, and how best to lower future cancer risk with drug treatments or even lifestyle changes such as weight loss and exercise.</p>
<p>Breast cancer screening undoubtedly <a href="http://cancerscreening.gov.au/internet/screening/publishing.nsf/Content/breastscreen-n-you-html">has benefits</a> but the size of these benefits is debated. A <a href="http://www.breast-cancer-research.com/content/17/1/63">recent review from the United Kindom</a> suggested perhaps only one out of 15 women diagnosed with cancer by mammographic screening will be helped: </p>
<ul>
<li>three will die of breast cancer anyway</li>
<li>eight will likely have survived even if not treated until symptomatic</li>
<li>three have cancers that would not have manifested or killed them anyway</li>
<li>one will avoid breast cancer death. </li>
</ul>
<p>The Australian breast screening program probably offers better odds than this, with more frequent screens, excellent equipment, staff and quality assurance, and good access to care for the majority of Australians. </p>
<p>Only further research can unravel exactly which DCIS is really a risk to health and needs aggressive treatment, which DCIS may be a marker of future cancer risk and how we can modify this risk, and perhaps which DCIS is an indolent condition which will never affect a woman in her lifetime.</p>
<p>When deciding whether or not to go for a mammographic screening test, getting balanced comprehensive information is important. Working out your individual cancer risk (via <a href="http://canceraustralia.gov.au/affected-cancer/cancer-types/breast-cancer/your-risk/calculate">calculators such as this</a>) and what you can do about it may help inform not only your screening choices but also your lifestyle choices which in turn can help prevent a number of diseases. </p>
<p>Understanding your individual risk also relies on emotions, anecdote and personal experience; this all feeds into decision-making. </p>
<p>However, choice does not solve the fundamental dilemma of screening: is it ethically acceptable to cause serious harm in some people in order to improve the prognosis of others?</p><img src="https://counter.theconversation.com/content/46624/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christobel Saunders 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>We’re told that finding symptoms of disease early will prevent the more serious consequences. But for pre-cancerous lesions, also known as stage 0 breast cancer, the picture is much more complicated.Christobel Saunders, Professor of Surgical Oncology, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/405472015-04-26T19:30:42Z2015-04-26T19:30:42ZExplainer: why do some breast cancers come back?<figure><img src="https://images.theconversation.com/files/79229/original/image-20150424-14577-19n6s36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">For 10% of patients the disease will return.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-128042738/stock-photo-close-up-topless-woman-body-covering-her-breast-with-hand-color-processed.html?src=qKEmezOFR3KtJpuVUwwqlQ-1-13">Fotos593/Shutterstock</a></span></figcaption></figure><p>Cancer is a collection of many hundreds of diseases. The common factor is that once-normal cells have undergone a series of mutations in their genes that has led to uncontrolled growth and an impaired ability to die when they normally should. </p>
<p>Cancers may also spread into other organs, forming secondary cancers, called metastases. When patients die of cancer, it’s usually due to these metastases. </p>
<p>Breast cancer is one of the most common cancers in the Western world, with 15,000 women (and about 70 men) <a href="http://www.aihw.gov.au/cancer/breast/">diagnosed each year</a> in Australia. Fortunately, with modern treatments, more than 90% of women with breast cancer go on to have a normal life expectancy, though the side effects of both the cancer and its treatment affect <a href="http://www.canceraustralia.gov.au/affected-cancer/cancer-types/breast-cancer/breast-cancer-statistics">many aspects</a> of their lives.</p>
<p>When detected, cancer can be classified into stages, based on how advanced the disease is in the body. </p>
<p>In breast cancer, the important factors include the aggressiveness of the cells (the grade) and specific proteins that they make. These proteins drive the growth of the tumour cells, including some that bind to female hormones such as oestrogen and growth-promoting proteins such as HER2. Whether a tumour has involved lymph nodes under the arm is also of great importance in assessing its likely potential to spread further.</p>
<p>These markers guide us closely in what drug treatments to consider but also suggest a “prognosis” – that is, how likely the cancer is to be cured or to come back.</p>
<p>So, a patient with breast cancer may undergo surgery to remove the lump and any involved lymph nodes, radiotherapy to try to ensure the cancer does not come back in the breast or lymph nodes nearby, and drug treatments that depend on these markers of aggressiveness. This is done as an “insurance” to increase the chances that the tumour never returns. Scans such as computed tomography (CT scans) are not usually helpful to monitor for recurrence, as small numbers of tumour cells can still be present, but cannot be seen.</p>
<p>Yet for 10% of patients the disease will return – often many years later – and this person is likely to die eventually of cancer. Even though other treatments may shrink the cancer, they cannot get rid of it all together, so unfortunately cure is not possible.</p>
<p>It is assumed that before this recurrence occurs, tiny microscopic nests of cancer cells are lying dormant somewhere in the body. A major quest for cancer researchers has therefore been to find where these cells are hiding and what causes them to wake up and cause secondary cancer.</p>
<p>One intriguing observation has been that in up to 10% of patients previously treated for cancer who are apparently “cancer free”, very careful examination of both blood and bone marrow <a href="http://journal.frontiersin.org/article/10.3389/fonc.2015.00042/abstract">reveals</a> a few residual cancer cells. This is strongly linked with a more likely chance of cancer coming back. </p>
<p>However, this is not universal. And we know that many supposed cancer cells floating in the bloodstream will in fact be mopped up by the bodies’ immune system or will die “of natural causes”. So, can we better define which are which?</p>
<p>One promising feature under intense scientific scrutiny is the so-called <a href="http://www.medilexicon.com/medicaldictionary.php?t=15716">mesenchymal</a> state of the cells. This indicates the cancer cells have changed from looking even less like their cell of origin – in this case, a breast cell – to more primitive cells that can move uninhibited in blood and spread through tissues. This is the same process the body uses in developing embryos and in other situations such as wound healing. </p>
<p>These mesenchymal features allow cancer cells to survive in the toxic environment of the bloodstream, to evade many of our current treatments such as chemotherapy and to set up home in distant organs – the process of metastasis, or secondary cancers.</p>
<p>We still don’t know what causes cancer cells to undergo mesenchymal change (termed <a href="http://www.ncbi.nlm.nih.gov/pubmed/25506895">epithelial-mesenchymal plasticity</a> or EMP), but understanding it means we are a step closer to developing drugs that can modify or stop the process. It also takes us closer to identifying a biomarker, so we can determine which patient may benefit from these as-yet-undeveloped drugs.</p><img src="https://counter.theconversation.com/content/40547/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christobel Saunders has previously received grants from NHMRC, National Breast Cancer Foundation and Cancer Council WA.</span></em></p><p class="fine-print"><em><span>Rik Thompson receives funding from the National Breast Cancer Foundation, the NHMRC and Princess Alexander Hospital Foundation.</span></em></p><p class="fine-print"><em><span>Robin Anderson receives funding from NHMRC, National Breast Cancer Foundation, Cancer Australia, Cancer Council Victoria. </span></em></p><p class="fine-print"><em><span>Anthony Dowling 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>Breast cancer is one of the most common cancers in the Western world, with 15,000 women (and about 70 men) diagnosed each year in Australia.Christobel Saunders, Professor of Surgical Oncology, The University of Western AustraliaAnthony Dowling, Medical Oncologist, St Vincent's Hospital Melbourne; Lecturer, The University of MelbourneRik Thompson, Professor of Breast Cancer Research, Institute of Health and Biomedical Innovation and School of Biomedical Sciences,, Queensland University of TechnologyRobin Anderson, Associate Professor, Peter MacCallum Cancer CentreLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/395532015-04-01T15:49:13Z2015-04-01T15:49:13ZCan elusive cancer stem cells seed new tumours months after chemotherapy?<figure><img src="https://images.theconversation.com/files/76596/original/image-20150331-1277-n47uuq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Lung cancer cells move in.</span> <span class="attribution"><span class="source">Cancer by Shutterstock</span></span></figcaption></figure><p>There is a theory among doctors and researchers that has divided the field of cancer treatment in recent years. It suggests that within a tumour there is a small group <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810531/">of special cancer seed cells</a> that are able to resist chemotherapy and bring about the return of the cancer many months after treatment has been completed. This “cancer stem cell” theory may explain the unfortunate relapses seen with many cancer suffers and the tragic consequences for the patient and their family.</p>
<p>These cancer seed cells resemble so-called stem cells that normally renew the cells in our tissues and organs throughout our lives. Stem cells are very specialised parent cells that have the potential to turn into many cell types such brain, liver, brain, blood and so on. While we’re used to hearing about how stem cells are the saviour of modern medicine, cancer stem cells <a href="http://ludwigcenter.stanford.edu/overview/theory.html">instead reproduce and sustain</a> the cancer. </p>
<p>So while with the potential to treat untreatable illnesses and to reverse the damage done by conditions such as stroke and spinal column injury, cancer stem cells on the other hand are a potential problem for the successful treatment of malignant disease. </p>
<p>In fact, if the cancer stem cell hypothesis is correct, they are <a href="http://www.nature.com/labinvest/journal/v86/n12/full/3700488a.html">the root of the disease</a>, which must be completely removed to ensure that the cancer does not grow back.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/76501/original/image-20150330-1249-pw571g.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/76501/original/image-20150330-1249-pw571g.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=445&fit=crop&dpr=1 600w, https://images.theconversation.com/files/76501/original/image-20150330-1249-pw571g.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=445&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/76501/original/image-20150330-1249-pw571g.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=445&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/76501/original/image-20150330-1249-pw571g.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=559&fit=crop&dpr=1 754w, https://images.theconversation.com/files/76501/original/image-20150330-1249-pw571g.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=559&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/76501/original/image-20150330-1249-pw571g.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=559&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Cancer stem cells.</span>
<span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File:Cancer_stem_cells_text_resized.svg">Peter Znamenskiy/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>The image above, where the yellow cell is a chemotherapy-resistant cancer stem cell, illustrates how cancer stem cells might also help cancer return in a patient who has undergone conventional cancer therapy. </p>
<h2>Targeting these rare cells</h2>
<p>Cancer stem cell theory suggests that conventional chemotherapy kills the majority of cancer cells but leaves rarer cancer stem cells alive. These stem cells ultimately reseed the tumour, which results in the cancer returning. So if the theory is correct then it should be possible to more effectively treat cancers by targeting cancer stem cells with specific drugs. </p>
<p>These drugs could be used in two ways. Rather than attacking all of the tumour cells at once, as is the case for traditional cancer therapy, specific drugs targeted at cancer stem cells should result <a href="http://www.nature.com/aps/journal/v34/n6/full/aps201327a.html">in the tumour slowly shrinking</a>, since the stem cells will no longer be there to replenish cells that naturally die within the cancer. However, this may take some time and a faster approach might be to use a combination of targeted cancer stem cell drugs along with conventional chemotherapy.</p>
<h2>Theory and reality</h2>
<p>Cancer stem cell theory looks incredibly exciting as a target for the treatment of cancer and as an explanation for the clinical relapses often seen in patients with metastatic cancer following conventional treatments. However, we must observe caution, as many scientists <a href="http://www.sciencedirect.com/science/article/pii/S1934590909000587who/">are sceptical</a> about <a href="http://www.ncbi.nlm.nih.gov/pubmed/19858069">the very existence</a> of these specialised stem cells within a cancer. Other researchers believe that even if cancer stem cells do exist in some form, targeting them <a href="http://celltrials.info/2008/12/28/validity-of-the-cancer-stem-cell-concept-under-discussion/">will not bring about</a> the spectacular cures that patients and families are hoping for. </p>
<p>Thankfully, there are some supporters of the theory who are willing to be the risk takers. A number of bioscience companies and universities have committed to clinical trials <a href="http://www.cancer.gov/clinicaltrials/search/view?cdrid=732286&version=HealthProfessional">for new drugs that specifically attack</a> cancer stem cells. The challenge for the scientists and clinicians involved in these trials will to show unequivocally that cancer stem cells are a reality and to prove that these drugs can be effective in treating and preventing re-occurrence of a cancer.</p>
<p>The hope is that in the coming years a wealth of information will become available from the current batch of clinical trials, aimed at utilising targeted cancer stem cell therapeutics. It remains to be seen if the results obtained in these trials will be enough to convince the sceptics that these stem cells actually exist in a tumour. On the other hand, if the targeted treatments are successful in preventing the return of cancer cells in children and adults, then we’ll have some indication beyond a reasonable doubt that the theory is correct.</p><img src="https://counter.theconversation.com/content/39553/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Pye 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 theory that some rare cancer cells aren’t caught by conventional chemotherapy has divided the field.David Pye, Scientific Director of the Kidscan Childrens Cancer Research Charity, University of SalfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/344552014-11-21T06:02:07Z2014-11-21T06:02:07ZClumped cancer cells spread more efficiently through the body than lone ones<figure><img src="https://images.theconversation.com/files/65116/original/image-20141120-4475-1d3fa9n.jpg?ixlib=rb-1.1.0&rect=6%2C456%2C4114%2C2288&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Better together.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/dellspics/13966371556/">dellspics</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p>Nine out of ten cancer patients die because cancer cells enter the blood circulation, spread and form tumours at distant organs. In circulation, cells can move individually or in a cluster. It is <a href="http://technical.sanguinebio.com/epithelial-to-mesenchymal-transition-the-key-to-cancer-metastasis/">believed</a> that cells moving individually pose the highest risk of forming tumours and are the primary “villains”. </p>
<p>A recent study we published in the <a href="http://rsif.royalsocietypublishing.org.ezproxy.rice.edu/content/11/101/20140962">Journal of Royal Society Interface </a> shows that this may not be true. Instead, cells that move in a cluster might be the primary “villains”, hence asking for new ways of fighting the spread of cancer.</p>
<p>Cells in most primary tumours are usually immovable and tied to each other. But some of them lose their adhesion and start invading their neighbouring tissue, gaining access to blood vessels and entering circulation. </p>
<h2>All in it together</h2>
<p>A few cells that move individually also attain <a href="http://www.ncbi.nlm.nih.gov/pubmed/18485877">special properties</a> that allow them to adapt to a new environment and seed a new tumour there. These traits are similar to the traits of stem cells – that’s why these cells are called as ‘Cancer Stem Cells’. They are resistant to all current cancer therapies, and can start a new tumor in any organ. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/65120/original/image-20141120-4484-q8y4dy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/65120/original/image-20141120-4484-q8y4dy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/65120/original/image-20141120-4484-q8y4dy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/65120/original/image-20141120-4484-q8y4dy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/65120/original/image-20141120-4484-q8y4dy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/65120/original/image-20141120-4484-q8y4dy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/65120/original/image-20141120-4484-q8y4dy.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">Brain metastasis.</span>
<span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File:Brain_metastasis_-_high_mag.jpg">Nephron</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We found that cells moving collectively are more likely to become Cancer Stem Cells and thus are the primary “villains” of metastasis – the spread of cancer to different organs. This occurs because the mechanism by which cancer cells decide to move collectively also triggers the mechanism which converts it into stem cells, but if cancer cells decide to move individually, their mechanism to gain properties of stem cells can be shut down. Therefore, cells moving in a cluster in the bloodstream pose a much higher risk of starting a new tumour at a distant organ than those moving individually.</p>
<p>This finding means that to fight metastasis, we need new drugs that can breakdown clumps of cancer cells, not lone agents. </p>
<h2>Team work has benefits</h2>
<p>Posing a higher risk of metastasis is not the only advantage of moving collectively for a cancer. Cells moving individually in circulation <a href="http://www.ncbi.nlm.nih.gov/pubmed/25171411">die more frequently</a> than those moving as a cluster, thus more clusters than individual cells reach the metastatic site. </p>
<p>Also, when these cells grow into a new tumour, they need to settle down in their new place quickly. This is because cells can’t multi-task efficiently – they can either divide or move. After reaching the new site, they want to start dividing, and doing that is much easier for cells moving collectively. They adhere to each other, rather than find something settle down.</p>
<p>Leaving their primary home, surviving in the harsh conditions in the human bloodstream, and then settling down and seeding a new home (a secondary tumor) at a distant organ, is not easy. And cancer seems to prepare its “soldiers” well for this by instructing them to move in a group or cluster. </p>
<p>Collective migration of cells is a well-planned strategy adopted by cancer for its utmost benefit – cells moving collectively die less in circulation, find it easy to settle down in a new organ, and most importantly, are more drug-resistant and potent to start a new tumour.</p><img src="https://counter.theconversation.com/content/34455/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>Nine out of ten cancer patients die because cancer cells enter the blood circulation, spread and form tumours at distant organs. In circulation, cells can move individually or in a cluster. It is believed…Mohit Kumar Jolly, Graduate student in Cancer Systems Biology, Rice UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/293052014-07-18T05:30:31Z2014-07-18T05:30:31ZStitching mice together reveals how ovarian cancer spreads<figure><img src="https://images.theconversation.com/files/54136/original/3rcpzg78-1405607385.jpg?ixlib=rb-1.1.0&rect=0%2C91%2C2186%2C1704&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Not cancer's only target.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/hey__paul/6122874024/">hey__paul</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Ovarian cancer is the fifth highest killer in women when it comes to cancer, according to statistics from the <a href="http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-key-statistics">American Cancer Society</a>, with about 14,000 deaths in the United States alone this year. The disease is particularly nasty because it starts to spread to other tissues much earlier than other cancers do.</p>
<p>Once the spread starts, the tissue that suffers first tends to be belly fat. Previously it was thought this spreading occurred through simpler means. However, new research published in the journal <a href="http://www.cell.com/cancer-cell/abstract/S1535-6108(14)00192-5">Cancer Cell</a> shows that the spreading actually happens via the blood. This could help develop new ways to prevent the spread.</p>
<p>The fatty tissue in the abdomen is a prime target for ovarian cancer cells because they produce a protein called NRG1. Once cancer cells have access to NRG1, they activate another protein, called HER3, which lets them multiply rapidly. Once the spread begins to the fat cells in the abdominal area, cancer cells can spread easily to the liver or lungs. </p>
<p>Since that abdominal area is so close to the ovary, researchers had assumed that the cancer cells simply detach from the ovary and float in the fluid filling the area till they reach the abdominal area. Yet, doctors would often observe that patients had tumours at the side of the fatty tissue that was quite far away from the ovary. Sometimes patients would show metastatic tumours in other organs like the liver or lungs but not in the abdominal area surrounding the ovary. Could it be that cancer cells were also using blood vessels to make their escape?</p>
<p>Researchers at MD Anderson Cancer Centre of the University of Texas, led by cancer biologist <a href="http://faculty.mdanderson.org/Anil_Sood/">Anil Sood</a>, came up with an innovative experiment to find the route cancer cells take. They physically joined two mice by stitching their skin together from hip to shoulder. After the surgery, the two mice ended up sharing a common blood circulatory system with their blood vessels fusing. </p>
<p>One of the mice among the artificially conjoined twins was made to develop ovarian cancer. If only the twin with ovarian cancer saw a spread of cancer to the abdominal area, it would prove that the previous theory about how ovarian cancer spread was right. But, instead, if the both twins saw development of cancer in their respective abdominal area, then the only way that could happen was through spreading via the blood.</p>
<p>Sood’s observation confirmed the latter scenario. Since the healthy twin’s abdomen was not physically close to the diseased ovary but still develop cancer, those cancer cells must have spread via the blood.</p>
<p>Interestingly, comparing the cancer cells that reached the healthy twin with the ones in the diseased ovary, the researchers found the travelling cancer cells were producing high amounts of a protein called HER3. In fact, cancer cells with more HER3 formed larger tumours in the abdominal area. And reducing the amount of HER3 protein in the cancer cells shrank the tumours in that area.</p>
<p>Sood thinks what preferentially brought the cancer cells to the healthy twin’s abdominal fat was the NRG1 protein, which then switches on HER3. To confirm that this happens in humans too, Sood checked patient records and found that those who had higher levels of HER3 protein in the tumour succumbed to the disease faster. </p>
<p>The discovery could help in developing better treatments. HER3 is a close cousin of the protein HER2 that is famous for being a drug target in breast cancer. Drugs that block HER2 may work against HER3 as well. In fact, a drug called pertuzumab, developed for breast cancer patients with high levels of HER2, is currently undergoing <a href="http://clinicaltrials.gov/show/NCT01684878">clinical trials</a> for patients with ovarian cancer, conducted by Hoffmann-La Roche. </p>
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<p><em>Next, read this: <a href="https://theconversation.com/now-we-know-why-drugs-dont-work-on-pancreatic-cancer-28420">Now we know why drugs don’t work on pancreatic cancer</a></em></p><img src="https://counter.theconversation.com/content/29305/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anwesha Ghosh 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>Ovarian cancer is the fifth highest killer in women when it comes to cancer, according to statistics from the American Cancer Society, with about 14,000 deaths in the United States alone this year. The…Anwesha Ghosh, PhD student in Biology, University of RochesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/221452014-02-10T05:52:18Z2014-02-10T05:52:18ZCancer cells use body’s wound-healing mechanism to spread<figure><img src="https://images.theconversation.com/files/41037/original/rk4c93mc-1391791181.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Moving cancer cells.</span> <span class="attribution"><span class="source">Wellcome Library</span></span></figcaption></figure><p>Metastasis, the spread of cancer cells from a primary tumour to different organs, is responsible for more than 90% of deaths due to cancer. Current treatments such as chemotherapy or radiotherapy are effective against primary tumours, but they cannot stop or kill the circulating cancer cells in the bloodstream. This means that understanding how cancer cells start to metastasise is crucial for developing new anti-metastasis therapies. </p>
<p>Now, researchers at Rice University (including myself) have <a href="http://www.pnas.org/content/early/2013/10/23/1318192110.abstract">deciphered</a> how a network of genes allows cancer cells to “decide” when to metastasise, thus opening up new therapeutic avenues.</p>
<p>Cancer cells in a primary tumour are usually fixed and immovable (sessile). However, if some of the cancer cells from the primary tumour start to invade neighbouring healthy tissue and enter the bloodstream to spread to different organs, it is bad news for the patient, because each one of these circulating cancer cells is capable of giving rise to a new tumour elsewhere in the body. Every cancer cell in the primary tumour either stays bound to its neighbours or metastasises. This decision is taken by a network of genes that functions as a switch, allowing each cell to either be “on” (migrating) or “off” (not migrating).</p>
<p>We discovered that this genetic switch also allows for a third choice that lies somewhere between “on” and “off”: cancer cells can move collectively, or migrate while still bound to their neighbours. These findings are crucial, because they underline a striking similarity in the collective cell migration of cancer cells and the kind of cell migration seen during wound healing. </p>
<p>This means that anti-metastasis strategies must be developed while keeping in mind that they do not inhibit wound healing. Even more care should be taken as the wound-healing drugs should not promote metastasis, in case a tumour is present.</p>
<h2>Switch to spread</h2>
<p>After circulating, cancer cells exit the bloodstream to settle at a distant organ. They switch back to being sessile and start growing another tumour at that organ. We show that moving collectively is advantageous to the cancer cells, because it is much easier for collectively moving cells rather than individually moving cells to switch back to a sessile state at a distant organ and start growing another tumour.</p>
<p>The metastasis “decision switch” consists of two specialised pairs of proteins, namely (SNAIL and microRNA34) and (ZEB and microRNA200). Both pairs are “mutually inhibitory”, with each partner in a pair inhibiting the production of the other. Imagine two people, A and B, who hate each other and refuse to attend a party where the other is present. Therefore, usually, in such pairs, one gets only two possibilities: either only A attends or only B attends – the concentration of the first protein is high and the second low, or vice-versa. In sessile cancer cells, the concentration of microRNAs is higher and that of ZEB and SNAIL low, and vice-versa for individually migrating cells.</p>
<p>The simple explanation then would be that these mutually inhibitory pairs behave as a switch, allowing for an “on” and an “off” state. However, our study shows that they actually behave as two switches, allowing for three possibilities. This they do because depending on the strength of inhibition (or degree of hatred) and other regulations (such as self-activation), such pairs can behave differently from being a usual two-way switch. </p>
<p>SNAIL and microRNA34 inhibit each other weakly. As a result, they both can be present at the same time (without driving any of them to extinction), with their exact amounts being decided by interactions with other genes – allowing three cases – A present, B absent; B present, A absent; and both A and B present under certain conditions. </p>
<p>It is the dance of these two pairs of proteins which allows cancer cells to have a three-way switch, rather than the previously thought two-way switch. Since this decision-making switch is common across cancers that originate in breast, prostate, colon, or pancreas, the results are potentially of importance for more than 60% of all cancer patients. </p>
<p>This process is remarkably similar to the body’s repair mechanism, where group of skin cells move to close a surface wound. Their collective movement allows the wound to be healed. Using this strategy often means they gain the best of both worlds – cell-cell cooperation to spread and uncontrolled growth. Knowing this process can enable us to better tackle metastasis, one of the most critical areas of cancer research and future treatment.</p><img src="https://counter.theconversation.com/content/22145/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>Metastasis, the spread of cancer cells from a primary tumour to different organs, is responsible for more than 90% of deaths due to cancer. Current treatments such as chemotherapy or radiotherapy are effective…Mohit Kumar Jolly, Graduate student in Cancer Systems Biology, Rice UniversityLicensed as Creative Commons – attribution, no derivatives.