tag:theconversation.com,2011:/id/topics/cancer-cell-8247/articlesCancer cell – The Conversation2023-01-16T16:05:12Ztag:theconversation.com,2011:article/1977682023-01-16T16:05:12Z2023-01-16T16:05:12ZStopping the cancer cells that thrive on chemotherapy – research into how pancreatic tumors adapt to stress could lead to a new treatment approach<figure><img src="https://images.theconversation.com/files/504479/original/file-20230113-18-eznoq2.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2414%2C2117&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Hypoxia, or a state of low oxygen, can encourage tumors to spread. This microscopy image visualizes the microenvironment of a breast tumor.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/HJpd72">Steve Seung-Young Lee, Univ. of Chicago Comprehensive Cancer Center, National Cancer Institute, National Institutes of Health via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>As with weeds in a garden, it is a <a href="https://www.cancerresearchuk.org/about-cancer/what-is-cancer/why-some-cancers-come-back">challenge to fully get rid of cancer cells</a> in the body once they arise. They have a relentless need to continuously expand, even when they are significantly cut back by therapy or surgery. Even a few cancer cells can give rise to new colonies that will eventually outgrow their borders and deplete their local resources. They also tend to wander into places where they are not welcome, creating metastatic colonies at distant sites that can be even more difficult to detect and eliminate.</p>
<p>One explanation for why cancer cells can withstand such inhospitable environments and growing conditions is an old adage: What doesn’t kill them makes them stronger.</p>
<p>At the very earliest stage of tumor formation, even before cancer can be diagnosed, individual cancer cells typically find themselves in an environment lacking nutrients, oxygen or adhesive proteins that help them attach to an area of the body to grow. While most cancer cells will quickly die when faced with such inhospitable conditions, a small percentage can adapt and gain the ability to initiate a tumor colony that will eventually become malignant disease. </p>
<p><a href="https://scholar.google.com/citations?user=e_INeP8AAAAJ&hl=en">We</a> <a href="https://scholar.google.com/citations?user=4Y2R_IgAAAAJ&hl=en">are</a> <a href="https://scholar.google.com/citations?user=e22ajL0AAAAJ&hl=en">researchers</a> studying how these microenvironmental stresses affect tumor initiation and progression. In our <a href="https://www.nature.com/articles/s41556-022-01055-y">new study</a>, we found that the harsh microenvironments of the body can push certain cancer cells to overcome the stress of being isolated and make them more adept at initiating and forming new tumor colonies. Moreover, these cancer cells may adapt even better in the inhospitable and stressful conditions they encounter while trying to establish metastases in other areas of the body or after they are challenged by treatment with chemotherapy or surgery. </p>
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<figcaption><span class="caption">The microenvironment of a cell can significantly influence its function.</span></figcaption>
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<h2>Cancer cells overcoming isolation stress</h2>
<p>We focused on <a href="https://doi.org/10.1001%2Fjama.2021.13027">pancreatic cancer</a>,
one of the most lethal cancers and one that is notoriously resistant to chemotherapy and often not curable with surgery. <a href="https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html">Almost 90%</a> of pancreatic patients will succumb to cancer recurrence or metastasis within five years after diagnosis. </p>
<p>We wanted to study how tumor formation is affected by what we call “<a href="https://www.nature.com/articles/s41556-022-01055-y">isolation stress</a>,” when cells are deprived of nutrients or oxygen supply because of poor blood vessel formation or because they cannot benefit from making contact with nearby cancer cells. To study how cancer cells respond to these situations, we recreated different forms of isolation stress in cell cultures, in mice and in patient samples by depriving them of oxygen and nutrients or by exposing them to chemotherapeutic drugs. We then measured which genes were turned on or off in pancreatic cancer cells.</p>
<p>We found that pancreatic cancer cells challenged with conditions that mimic isolation stress gain a new receptor on their surface that unstressed cancer cells don’t typically have: <a href="https://doi.org/10.1016/j.bbrc.2015.03.169">lysophosphatidic acid receptor 4, or LPAR4</a>, a protein involved in tumor progression. </p>
<p>When we forced the cancer cells to produce LPAR4 on their surfaces, we found that they were able to form new tumor colonies two to eight times faster than average cancer cells under isolation stress conditions. Also, preventing cancer cells from gaining LPAR4 when they were stressed reduced their ability to form tumor colonies by 80% to 95%. These findings suggest that the ability of cancer cells to gain LPAR4 when they are exposed to stress is both necessary and sufficient to promote tumor initiation.</p>
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<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>
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<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>
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<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>
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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>
</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>
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<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/1692622021-10-06T19:01:35Z2021-10-06T19:01:35ZWe created a microscope slide that could improve cancer diagnosis, by revealing the ‘colour’ of cancer cells<figure><img src="https://images.theconversation.com/files/424927/original/file-20211006-27-1r03a5g.jpeg?ixlib=rb-1.1.0&rect=31%2C18%2C1478%2C1113&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption"></span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><p>When we look at biological cells under a microscope, they’re usually not very colourful. Normally, to visualise them we have to artificially add colour — typically by staining. By doing so, we can see their shape and arrangement in a tissue and determine whether they’re healthy or not. </p>
<p>Sometimes, though, cell structure alone isn’t enough to accurately identify disease — which can lead to misdiagnosis and potentially fatal consequences for a patient. But what if there was a way to not only see the structure of cells, but also determine whether they are abnormal, simply by looking at their intrinsic colour under a microscope? </p>
<p>This was our team’s goal as we developed a new medical diagnostic tool called the NanoMslide. We modified a standard microscope slide to turn it into a powerful tool for breast cancer detection. Our <a href="https://www.nature.com/articles/s41586-021-03835-2">research</a> is published today in Nature.</p>
<h2>Early detection is key</h2>
<p>It’s <a href="https://www.canceraustralia.gov.au/cancer-types/breast-cancer/statistics">estimated</a> one in eight Australian women will be diagnosed with breast cancer by age 85. As with most cancers, catching the disease early is critical. However, an accurate diagnosis of the earliest stages of breast cancer requires identifying small numbers of diseased cells throughout a tissue, which can be incredibly challenging. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Human cancerous tissue viewed under miscroscope" src="https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Human cancerous tissue, viewed through a microscope with the NanoMslide applied.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Normal (non-cancerous) human tissue, viewed through a microscope with the NanoMslide applied.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>The NanoMslide can manipulate light at the nanoscale, causing cells to “light up” with vivid colour contrast. This makes it easier to recognise potentially cancerous cells (or benign abnormalities) within the tissue. </p>
<p>By providing a way to instantly distinguish which cells could be cancerous, the tool may help to reduce current uncertainty around very early-stage breast cancer detection. With mammogram screening, distinguishing breast abnormalities from early breast cancers upon biopsy is very important, particularly as misdiagnosis rates can be as high as 15%.</p>
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Read more:
<a href="https://theconversation.com/devastated-and-sad-after-36-years-of-research-early-detection-of-ovarian-cancer-doesnt-save-lives-160999">'Devastated and sad' after 36 years of research — early detection of ovarian cancer doesn't save lives</a>
</strong>
</em>
</p>
<hr>
<h2>Major barriers in development</h2>
<p>Incorporating nanotechnology into medical diagnostics presents a number of challenges. It took us six years of development to ensure NanoMslide would work effectively. In the end it was a combination of cutting-edge nanofabrication, a significant amount of trial-and-error and a bit of good fortune that led to our breakthrough.</p>
<p>For decades, researchers have known cancer cells tend to interact with light in a way that’s different to healthy cells. This is due to a variety of factors, such as the distribution of protein inside the cell and differences in its overall shape. </p>
<p>The main challenge is these differences can be extremely subtle and can present in a variety of ways. Previous approaches to differentiating cancer cells (without using stains or labels) have tended to use specialised microscopy equipment, or complex techniques. </p>
<p>But these approaches are difficult to incorporate into existing pathology workflows and can require specialist training and knowledge. So we took a radically different approach. </p>
<h2>Success with human tissue</h2>
<p>Rather than focusing on developing a better microscope, we focused on improving the microscope slide instead. </p>
<p>By developing a special nanofabricated coating, we modified the surface of an ordinary microscope slide and transformed it into one huge sensor. What’s truly remarkable is the structures of the sensor are just a few hundred nanometres across, yet are repeated with amazing precision across an area of tens of centimetres, or more. </p>
<p>Maintaining this level of precision, which is necessary for reliable fabrication at this scale, has taken advances in nanofabrication techniques that have only become commercially available in the past six years.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=292&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=292&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=292&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=367&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=367&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=367&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 NanoMslide is a large sensor fitted with cutting-edge nanotechnology capabilities.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>The sensor is activated by visible light. And when an object such as a tissue or single cell comes into contact with the sensor’s surface, colours are produced. It is this feature which we’ve been able to optimise to allow pathologists to detect cells that are likely cancerous, just by looking at them.</p>
<p>The dyes which are currently used to stain tissues (to visualise cell shape and architecture) normally present as one or two colours. The NanoMslide renders tissues in beautiful full-colour contrast, making it easier to differentiate multiple types of cell on a single slide. </p>
<p>For our study, we tested the slides with expert breast-cancer pathologists, using both a mouse model and patient tissue. By starting with a well-characterised small-animal model, our team of physicists, cancer researchers and breast pathologists was able to develop the technology further. </p>
<p>We eventually reached the point where we could be confident some of the specific colours visible were indicative of cancerous cells. This led to further pathology assessments with patient tissue, where there is more complexity to contend with in terms of diagnosis. </p>
<p>Yet, even in this more challenging setting, the NanoMslide performed strongly. It also outperformed some commercial biomarkers, which are used as an aid for borderline diagnoses (where cancer is difficult to tell apart from benign abnormalities).</p>
<h2>Like going from black and white to colour television</h2>
<p>Because the technology doesn’t rely on any special function, or specific molecular interactions, it could potentially be applied to other types of cancer — even other types of disease. Another application now being worked on is to examine the results of liquid biopsies, such as cheek swabs, for immediate point-of-care analysis.</p>
<p>In April, we were fortunate to benefit from the opening of a new instrument at the Australian National Fabrication Facility to enable the scaling-up of production. This means NanoMslide can be moved from small-scale to medium-scale manufacture, allowing us to explore a number of different applications, and produce the numbers of slides required for further clinical validation. </p>
<p>The technology could also be hugely beneficial to the growing digital-pathology space, where the vivid colours generated by NanoMslide could help develop next-generation artificial intelligence algorithms to identify signs of disease. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-why-do-people-get-cancer-106069">Curious Kids: Why do people get cancer?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/169262/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brian Abbey receives funding from the Australian Research Council (ARC).</span></em></p><p class="fine-print"><em><span>Belinda Parker receives funding from the DHHS, National Breast Cancer Foundation, Prostate Cancer Foundation Australia, Movember, and the Peter MacCallum Cancer Foundation. </span></em></p>The NanoMslide causes potentially cancerous cells to ‘light up’ with vivid colour contrast. It has already been successful in finding early-stage breast cancer cells in human tissue.Brian Abbey, Professor of Physics, La Trobe UniversityBelinda Parker, Senior Faculty/Laboratory Head, Peter MacCallum Cancer CentreLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1109212019-02-04T12:30:28Z2019-02-04T12:30:28ZCancer growth in the body could originate from a single cell – target it to revolutionise treatment<figure><img src="https://images.theconversation.com/files/257009/original/file-20190204-193213-1tzdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/cancer-cells-3d-illustration-574815085?src=Bz5qM75AljUdBvqrlw6Bfg-1-3">Andrii Vodolazhskyi/Shutterstock</a></span></figcaption></figure><p>Cancer remains a frightening and largely incurable disease. The toxic side effects of chemotherapy and radiation make the cure often seem as bad as the ailment, and there is also the threat of recurrence and tumour spread.</p>
<p>Cancer treatment still follows a practically medieval method of cut, burn or poison. If the growth can’t be cut out through surgery, it may be burnt away with radiation or poisoned by chemotherapy. As a result, cancer therapy remains a daunting diagnosis for patients and treatment options seem limited for a disease which causes <a href="https://www.who.int/news-room/fact-sheets/detail/cancer">one in six deaths globally</a>.</p>
<p>The failure to innovate in cancer treatment may lie in the very poor success rate of clinical trials. Approximately 95%-98% of new anti-cancer drugs <a href="https://academic.oup.com/biostatistics/advance-article/doi/10.1093/biostatistics/kxx069/4817524">actually fail phase III clinical trials</a>, the phase in which <a href="https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-clinical-trials-are/phases-of-clinical-trials#phase3">new treatments are compared</a> with existing therapy options. This is a staggering statistic. No other business could possibly survive with such an abysmal success rate.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/257011/original/file-20190204-193213-reh2xh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/257011/original/file-20190204-193213-reh2xh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/257011/original/file-20190204-193213-reh2xh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/257011/original/file-20190204-193213-reh2xh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/257011/original/file-20190204-193213-reh2xh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/257011/original/file-20190204-193213-reh2xh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/257011/original/file-20190204-193213-reh2xh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Chemotherapy and radiotherapy are broad-based treatments which attack the bulk of cancer cells but also damage healthy tissue.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cancer-patients-receiving-chemotherapy-treatment-hospital-529109200?src=PhgS1fo7VEItjr0JsbMkcQ-1-0">Napocska/Shutterstock</a></span>
</figcaption>
</figure>
<p>Most drugs are made to target “bulk” cancer cells, but not the root cause: the cancer stem cell. Cancer stem cells, also known as “tumour-initiating cells”, are the only cells in the tumour <a href="https://www.nature.com/articles/nature09781">that can make a new tumour</a>. New therapies that specifically target and eradicate these cancer stem cells are needed to prevent tumours growing and spreading, but for that there needs to be more clarity around the target.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941316/">Our new research</a> may have discovered such a target. We have identified and isolated cells within different cancerous growths which we call the “cell of origin”. Our experiments on cancer cells derived from a human breast tumour found that stem cells – representing 0.2% of the cancer cell population – have special characteristics.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/drug-resistant-cancers-kill-millions-heres-how-were-tackling-them-78208">Drug-resistant cancers kill millions – here's how we're tackling them</a>
</strong>
</em>
</p>
<hr>
<p>They generate <a href="https://www.frontiersin.org/articles/10.3389/fonc.2018.00677/abstract">vast amounts of energy and proliferate rapidly</a>. We believe that they resemble the cancer cell of origin that has escaped senescence – the natural process of cell ageing and “death” which concludes a healthy cell life cycle. These are thought to be the first cancer cells which start the process of uncontrolled cell multiplication and cause tumours to form.</p>
<p>These cancer stem cells undergo anchorage-independent growth, also known as growth in suspension, without any tissue attachment. This is how metastasis occurs – spreading via the blood vessels and lymphatic vessels. These features put them front and centre as a new target for anti-cancer therapy.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/257018/original/file-20190204-193195-10koi98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Cancer stem cells grow in suspension in the bloodstream and spread throughout the body.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendering-red-blood-cells-vein-517874557?src=BvKWjBwOSlhDO4joRgHq1g-1-5">Phonlamai Photo/Shutterstock</a></span>
</figcaption>
</figure>
<p>With astonishing luck, these energetic cancer stem cells are colour-coded which means they have a natural phosphorescent glow, making them easy to identify and target.</p>
<p>Now that we have found them and we know how they behave, it should be relatively simple to find drugs to target cancer stem cells. <a href="https://www.frontiersin.org/articles/10.3389/fonc.2018.00677/abstract">In our new paper</a> we have already shown that they are easily targeted with a mitochondrial inhibitor or a cell cycle inhibitor <a href="https://www.breastcancercare.org.uk/information-support/facing-breast-cancer/going-through-breast-cancer-treatment/targeted-therapy/ribociclib-kisqali">such as Ribociclib</a>, an FDA-approved drug in the US which would prevent their proliferation. </p>
<p>Ultimately, this means that if we focus on energetic cancer stem cells, we may be able to directly hit the target. We might be able to turn cancer into a manageable chronic disease, like diabetes. We believe that we have arrived at the start of a new, more fruitful, road in cancer therapy. As a consequence, “big pharma” drug screening should actually focus on cancer stem cells and their relevant targets.</p><img src="https://counter.theconversation.com/content/110921/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael P. Lisanti holds a minority interest in Lunella Biotech, Inc.
</span></em></p>Cancer treatment could be revolutionised by the discovery of the origin cells which divide first.Michael P. Lisanti, Professor of Translational Medicine, University of SalfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1060692018-11-28T02:44:39Z2018-11-28T02:44:39ZCurious Kids: Why do people get cancer?<figure><img src="https://images.theconversation.com/files/247140/original/file-20181125-149311-j6g2ja.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A lot of people have spent a very long time wondering what causes cancer -- and scientists still can't say for certain why an individual person might have it.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/marinadelcastell/15123637900/in/photolist-p3qADA-attcLe-pGzdsK-97nH3D-2jpqDi-8fL2Zr-o5UP3n-8PVW7L-7ojh9A-7g1BVw-288wvGe-VFnJj1-gZtiT-d9FKxv-6gxECD-c2ZWYf-bxZCCW-7y4aZ-7NqN9e-bwAzyD-4Et28P-67FT3v-FdXFg4-26LD9mn-aYXvLv-dAeS22-peG81g-JV6R1a-4KxHrW-aAK5Ry-85pVPw-7Q79FC-fnoz5f-dy4QAh-6Jz4Hm-rmDhi-9JG5DX-9zTWFe-i15x3R-248k8yj-4oedpp-9LC5DU-gjY9U-8U3f5r-fnpAd7-jAnpRv-iVAF-WJ526X-3jjnDe-o1GsGu">Marina del Castell/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p><em>This is an article from <a href="https://theconversation.com/au/topics/curious-kids-36782">Curious Kids</a>, a series for children. The Conversation is asking kids to send in questions they’d like an expert to answer. All questions are welcome – serious, weird or wacky! You might also like the podcast <a href="http://www.abc.net.au/kidslisten/imagine-this/">Imagine This</a>, a co-production between ABC KIDS listen and The Conversation, based on Curious Kids.</em> </p>
<hr>
<blockquote>
<p><strong>Why do people get cancer? – Sascha, age 8, Hurstbridge, Victoria.</strong></p>
</blockquote>
<hr>
<p>This is a really tough question, Sascha. Lots of very clever people are working hard to try to answer it. I have worked on this problem for many years, and to be honest it still blows my mind to really think about just how complex it is.</p>
<p>Before we talk about <em>why</em> we get cancer, it helps to understand <em>how</em> we get cancer.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/interactive-body-map-what-really-gives-you-cancer-52427">Interactive body map: what really gives you cancer?</a>
</strong>
</em>
</p>
<hr>
<p>All living things are made of <a href="https://vimeo.com/259704641">tiny building blocks called cells</a>. In humans there are hundreds of different kinds of cells, all with special jobs to do. They build our various organs like our skin, brain and bones. Some cells (such as brain and bone) can live for many years, while others (like red blood cells) live only a few weeks.</p>
<p>A human body is made up of trillions of individual cells, many more than all the stars you can see in the night sky.</p>
<p>As we grow, our body needs to make new cells. And as cells get old or damaged, they die and need to be replaced. That helps to keep us healthy.</p>
<p>The simplest way to think of a cancer is that sometimes, one of those trillions of cells starts to grow out of control and refuses to die. This out-of-control cell then divides and makes millions of copies of itself. It can grow to form a tumour - or, in some cases such as leukaemia, spreads through our blood.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=202&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=202&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=202&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=253&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=253&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247627/original/file-20181127-32236-1lp9pv8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=253&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An out-of-control cell can divide and make millions of copies of itself, and can grow to form a tumour.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Cancer cells can also spread to other parts of our body where they would not normally be found. This can cause important organs to stop doing their job and make us very unwell, or die.</p>
<h2>Copying the code - and making mistakes</h2>
<p>The really incredible thing about cells is that they contain the instructions for making copies of themselves. These instructions are stored in a code called the genome, made of a quite beautiful chemical called DNA.</p>
<p>And if you took the DNA from all the cells in a human and lined it all up, it would stretch around the Moon and back six or seven times.</p>
<p>The alphabet cells use to write this DNA code is made of just four different chemical “letters”: A,C,T, and G. And the instructions in each cell are made of about 6 billion of these chemical letters, which need to be copied exactly every time a cell divides to make a copy of itself.</p>
<p>To help you understand this amazing feat of biology, imagine trying to copy the entire Harry Potter book series in handwriting a thousand times over. That’s what a cell needs to do every time it divides, and it’s happening millions of times every day in our bodies.</p>
<p>You can watch an animation of the incredible, tiny machine cells use to copy DNA here:</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/OjPcT1uUZiE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>With all that DNA to copy, cells are bound to make the occasional spelling mistake - we call these mistakes “mutations”. Sometimes, those mutations change the meaning of a cell’s instruction book, causing it to grow out of control and form a tumour. </p>
<p>This is what we call cancer.</p>
<h2>But why?</h2>
<p>Now, back to the question of <em>why</em> we get cancer.</p>
<p>Different scientists are having a bit of an argument over this question, but it seems to come down to a combination of bad luck and various experiences you might have in life. Things like too much sunshine, certain chemicals (such as tobacco smoke), alcohol, some foods and even some viruses can increase our chances of getting mutations in our DNA.</p>
<p>Because those mutations in DNA take time to build up, cancer is most commonly seen in older adults. Children do sometimes get cancer but thankfully it is relatively rare. Usually, evolution would mean not many people would get such a horrible disease like cancer. But because most people get cancer after they have had kids, evolution is almost blind to cancer. People who might have a higher cancer risk because of their genes live long enough to pass those genes onto their kids.</p>
<p>You can reduce your chance of cancer by making healthy, sensible lifestyle decisions but it is not possible to completely prevent it. Unfortunately, as I said before, it’s at least partly down to bad luck. </p>
<p>Importantly, we can almost never say for sure why an individual person has cancer.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-is-there-anything-hotter-than-the-sun-105748">Curious Kids: Is there anything hotter than the Sun?</a>
</strong>
</em>
</p>
<hr>
<p><em>Hello, curious kids! Have you got a question you’d like an expert to answer? Ask an adult to send your question to us. They can:</em></p>
<p><em>* Email your question to curiouskids@theconversation.edu.au
<br>
* Tell us on <a href="https://twitter.com/ConversationEDU">Twitter</a></em></p>
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<img alt="" src="https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em>Please tell us your name, age and which city you live in. You can send an audio recording of your question too, if you want. Send as many questions as you like! We won’t be able to answer every question but we will do our best.</em></p><img src="https://counter.theconversation.com/content/106069/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Darren Saunders receives funding from NHMRC, US DoD, and MNDRIA. He is secretary of Science and Technology Australia.</span></em></p>I have worked on this problem for many years, and to be honest it still blows my mind to really think about just how complex it is.Darren Saunders, Associate professor, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/853792017-10-24T00:14:14Z2017-10-24T00:14:14ZA new clue into treatments for triple negative breast cancer, a mean disease<figure><img src="https://images.theconversation.com/files/191238/original/file-20171020-13963-1w6ykal.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">African-American women are about three times more likely to be diagnosed with triple negative breast cancer, an aggressive form of the disease. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/breast-cancer-awareness-charity-race-multiethnic-152895665?src=qqKkirwMIeqVbzrIa7ABCw-1-15">mangostock/Shutterstock.com</a></span></figcaption></figure><p>When a woman finds a lump in her breast, her doctor’s first move is usually to recommend a biopsy – that is, to remove a small portion of the lump for analysis. If the lump is cancerous, doctors test for three different <a href="https://www.cancer.gov/types/breast/hp/breast-treatment-pdq">clinical markers</a>: estrogen receptor, progesterone receptor and human epidermal growth factor receptor. The results determine what kind of hormone or growth factor receptor treatment the patient receives.</p>
<p>About 15-20 percent of breast cancers, though, don’t test positive for any of the three markers. They’re called <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868264/">triple negative breast cancers</a>, and they’re big trouble. Treatments developed for cancers that test positive for any of the three different markers will not work on triple negative breast cancers.</p>
<p>Triple negative breast cancers are <a href="http://www.breastcancer.org/symptoms/diagnosis/trip_neg/behavior">more aggressive</a> and more likely to spread throughout the body. </p>
<p>At the 2017 <a href="https://www.tnbcconference.org">International Triple Negative Breast Cancer Conference</a> in Atlanta, I presented findings that show promise of improving treatment and outcomes for some women with the disease, even though more study is needed to confirm my findings.</p>
<h2>Moving the focus</h2>
<p>The <a href="http://www.breastcancer.org/symptoms/diagnosis/trip_neg/behavior">five-year survival rate</a> for women with triple negative breast cancer is lower – 77 percent – than the five-year survival rate – 93 percent – for women whose cancers have one of the three receptors. Also, because there are no hormone-targeted treatments for triple negative breast cancer, women often must endure harsher treatments like radiation and chemotherapy. Black women are about three times more likely than white women to develop triple negative breast cancer, a difference that could be due to their genetics.</p>
<p>Most researchers working on triple negative breast cancers study the tumor themselves. But my research looked at the disease from a different angle – the way the patient’s own body attacks the tumor. </p>
<p>When a woman gets breast cancer, her immune system leaps into gear. Her body sends <a href="https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=41004">tumor infiltrating lymphocytes</a> to target and kill the tumor cells. </p>
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<img alt="" src="https://images.theconversation.com/files/191239/original/file-20171020-13995-113b9r1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/191239/original/file-20171020-13995-113b9r1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/191239/original/file-20171020-13995-113b9r1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/191239/original/file-20171020-13995-113b9r1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/191239/original/file-20171020-13995-113b9r1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/191239/original/file-20171020-13995-113b9r1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/191239/original/file-20171020-13995-113b9r1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Lymphocytes attack a cancer cell.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-cancer-cell-lymphocytes-617973347?src=HaMn3Sbb-AvLldL421pibQ-1-0">Christoph Burgstadt/Shutterstock.com</a></span>
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<p>Researchers and I looked at 103 early-stage patients with triple negative breast cancer, 71 of them African-American and the rest European-American, to see whether there was a difference in tumor-infiltrating lymphocyte count. Tumor-infiltrating lymphocytes were evaluated in hemotoxylin- and eosin-stained tissue sections according to the International TILs Working Group 2014 guidelines by pathologists we collaborate with at Emory University Hospital. We found that the African-Americans had a <a href="http://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1090#.We5AEulbzww">significantly higher level of tumor infiltrating lymphocytes</a> in early-stage cancer than white women. </p>
<p>We also found higher tumor infiltrating lymphocyte levels in early-stage African-American patients who were diagnosed at a young age or tested negative for a fourth common clinical marker, androgen receptor. African-American women are more likely to be diagnosed with triple negative breast cancer at younger age and lack androgen receptor, factors associated with more aggressive disease, compared to white women.</p>
<p>Maybe most importantly, we found that we could use the level of tumor infiltrating lymphocytes to predict a greater or lower risk of death: The more tumor infiltrating lymphocytes, the better the survival we found among early-stage African-American cancer patients. High levels of tumor infiltrating lymphocytes also seem to correlate with higher levels of DNA damage within the tumor. If this correlation bears out in further research, doctors could use it to predict response to DNA repair therapies for a specific patient.</p>
<p>Finally, our study pointed to the possibility of an exciting new form of treatment: adoptive T cell therapy. In adoptive T cell therapy, doctors extract immune cells from a patient and genetically engineer them to expand the patient’s T cells. The cells are then infused back into the patient to improve her anti-tumor response.</p>
<h2>Promise in other cancer types</h2>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315690/">Adoptive cell therapy</a> has already shown promise in melanoma patients, and it is currently in clinical trials as a treatment option for breast cancer patients. From our research, we already know who might be most likely to respond to the treatment: African-American women, in the early stages of the disease, whose tumor infiltrating lymphocyte count is lower than normal. However, we plan to validate these results in additional patient cohorts.</p>
<p>Triple negative breast cancer is a scary disease – aggressive, rapid-spreading and insusceptible to the hormone treatments we use to target most breast cancers. But our next key to fighting it might not be in the tumor at all. It just might be tumor infiltrating lymphocytes, those tiny anti-cancer warriors our own bodies throw into the fray.</p><img src="https://counter.theconversation.com/content/85379/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nikita Wright does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers have long been looking for clues into how to treat triple negative breast cancer. Could fighter blood cells that infiltrate the tumor provide insight?Nikita Wright, Ph.D. Candidate, Biology, Georgia State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/496072015-11-02T14:13:42Z2015-11-02T14:13:42ZComplex sugar molecules may be the key to safer chemo<figure><img src="https://images.theconversation.com/files/100148/original/image-20151029-15365-1nqod8t.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">www.shutterstock.com</span></span></figcaption></figure><p>The ability to aim chemotherapy drugs at cancer cells - and just cancer cells - has been <a href="http://www.cancerprogress.net/timeline/targeted-drugs">a goal</a> for medical researchers for a long time. So is the recent discovery of a <a href="http://bit.ly/1WjKcrv">malaria protein</a> that appears to target the tumour and not the patient’s normal cells a significant step forward in the arms race against cancer? </p>
<p>Certainly the idea of targeting cancer cells with proteins that carry a toxic drug payload is not new. In fact, several of these <a href="http://www.cancer.gov/about-cancer/treatment/drugs/fda-brentuximabvedotin">“protein-drug complexes”</a> have been approved by the US Food and Drug Administration since 2011. Perhaps the most important difference between this latest discovery and the available protein-drug complexes is the target: a complex sugar molecule that is mainly found on cancer cells or the placenta of pregnant women and is largely absent in other normal human cells. </p>
<h2>Helpful malaria parasite</h2>
<p>The origin of the protein that binds to these sugars, in this case from the malaria parasite, may make <a href="http://www.dailymail.co.uk/health/article-3270894/Cancer-breakthrough-MALARIA-protein-destroy-nine-10-cancers.html">big headlines</a> but its source is largely irrelevant. It is the ability of a protein to distinguish between cancer cells and normal cells that will largely determine its fate as a drug delivery mechanism. </p>
<p>The ultimate goal of cancer drug discovery has always been linked to the ability to discriminate between normal and cancerous tissue. The ability of a drug to kill cancer cells and not normal cells would minimise the toxic side effects associated with traditional chemotherapy and allow higher doses to be used to speed up the destruction of the tumour. </p>
<p>Proteins can be used to home in on a target on the surface of cancer cells and deliver a drug-laden warhead. This requires a target on the surface of the cancer cells that isn’t present on normal tissue. Scientists have been searching for these targets for many years and many so-called targeted cancer treatments have been developed, with varying degrees of success. </p>
<p>The idea that one such cancer target might be found in the placenta of pregnant women, as is the case for this latest discovery, may seem at first glance to be rather bizarre. However, researchers have believed for many years that the secrets associated with the initiation and progression of cancer, may be hidden in the way that the foetus develops from a simple pre-embryonic clump of cells and the <a href="http://www.scientificamerican.com/article/cancer-clues-from-embryos/">changes that occur</a> in the placenta during the baby’s development in the womb.</p>
<p>Understanding some of these normal development processes might lead to a groundbreaking discovery in cancer research, such as has been reported by these researchers. In this instance, the protein found on the surface of the malaria parasite was found to bind to targets on the placenta. This allowed the parasite to associate itself with the placenta, which can lead to a common complication of malaria infection in pregnancy. But the subsequent discovery that it also binds to specific sugar targets on the surface of cancer cells was exploited by the scientists.</p>
<h2>Sugar carries important information</h2>
<p>Although largely neglected by the scientific community, over many years, complex sugars are rapidly being seen as some of the most <a href="http://www.ncbi.nlm.nih.gov/books/NBK1963/">important molecules</a> on the surface of normal and cancerous cells. In many ways the information carried by sugars is far more complex than that carried in the DNA of your genes. And perhaps the most important advance in this new study is really the sugar target itself.</p>
<p>Previous attempts to use complex sugars as a target for cancer treatment have had been encouraging, however, most of these have involved work in <a href="http://www.nature.com/nrd/journal/v9/n4/full/nrd3012.html">cancer vaccines</a>. So the identification of proteins that can seek out sugars only found on the surface of cancer cells could be a major step forward in our ability to target cancer with protein-drug complexes.</p>
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<img alt="" src="https://images.theconversation.com/files/100146/original/image-20151029-15365-13jha5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/100146/original/image-20151029-15365-13jha5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=445&fit=crop&dpr=1 600w, https://images.theconversation.com/files/100146/original/image-20151029-15365-13jha5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=445&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/100146/original/image-20151029-15365-13jha5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=445&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/100146/original/image-20151029-15365-13jha5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=559&fit=crop&dpr=1 754w, https://images.theconversation.com/files/100146/original/image-20151029-15365-13jha5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=559&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/100146/original/image-20151029-15365-13jha5t.jpg?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">
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<span class="caption">Animal studies aren’t perfect.</span>
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<p>So will this new “protein guided” drug delivery system really deliver cancer drugs to human tumours and minimise the risk of damage to the patient’s healthy tissue? Evidence from <a href="http://www.cell.com/cancer-cell/abstract/S1535-6108(15)00334-7">an experiment</a> with mice suggests that it will. Unfortunately, experiments on animals do not always translate into the successful treatment of patients, and we must be cautious in interpreting these kinds of findings. The number of different sugar structures on the surface of normal and cancerous cells is also vast and small differences can lead to their success or failure as a cancer-specific target. A relatively insignificant change in the structure of the sugars between the non-human models and patients could easily lead to the protein drug complex hitting normal cells as well as the cancer, causing considerable harm to the patient. </p>
<p>Although the results of this recent study are exciting, it will be a long time before we can determine its full impact on the field of targeted cancer treatment. Scientists and people with cancer will undoubtedly watch with great interest as these protein-drug complexes move into clinical trials.</p><img src="https://counter.theconversation.com/content/49607/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>Targeting the complex sugars on cancer cells is receiving renewed attention.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/492552015-10-16T14:01:13Z2015-10-16T14:01:13ZWhy antioxidants might actually make your cancer worse<figure><img src="https://images.theconversation.com/files/98658/original/image-20151016-25125-r8f3gv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Free radicals - misunderstood?</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Antioxidants have made a fortune for the dietary supplement industry, but how many people really know what they are and why they’re supposedly good for you? One common claim is that the these molecules <a href="http://www.ncbi.nlm.nih.gov/pubmed/15630252">can protect you</a> from cancer. This is supposedly because they can counteract other molecules known as “reactive oxygen species” or “free radicals” that can be created in our cells and then damage DNA, potentially leading to cancer.</p>
<p>But cells generate many different types and levels of free radicals. For example, some <a href="http://www.annclinlabsci.org/content/30/2/145.short">are used by the immune system</a> to attack pathogens. Therefore we don’t fully understand the benefits and dangers of wiping free radicals out with antioxidants. If we remove all free radicals we may be preventing their good actions. This may be why there’s little solid evidence that antioxidants actually reduce the risk of cancer or help to treat the disease. In fact, some <a href="http://scienceblog.cancerresearchuk.org/2009/10/02/antioxidants-and-cancer-%E2%80%93-the-plot-thickens/">large clinical trials</a> show the opposite.</p>
<p>My colleagues at King’s College London and I recently <a href="http://jnci.oxfordjournals.org/content/108/1/djv289.short">published research</a> in the Journal of the National Cancer Institute highlighting that free radicals are not just damaging agents. <a href="http://scienceblog.cancerresearchuk.org/2015/10/16/antioxidants-free-radicals-and-melanoma-spread-whats-going-on/">Our work</a> adds to the <a href="http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature15726.pdf">growing evidence</a> that antioxidant supplements can, in some circumstances, do <a href="http://stm.sciencemag.org/content/7/308/308re8">more harm</a> than good. </p>
<h2>Shaping cancer cells</h2>
<p><a href="http://news.bbc.co.uk/1/hi/health/7700264.stm">Back in 2008</a>, we showed that melanoma cells – the most serious form of skin cancer –- can change their shape depending on the amounts of two key opposing molecules called Rac and Rho that function like a switch. If there’s more Rac and less Rho, the cells become long and spindly. With more Rho and less Rac, the cells become rounder. <a href="http://scienceblog.cancerresear%20chuk.org/2014/06/25/science-snaps-how-skin-cancer-spreads-the-round-or-flat-of-it/">More recently</a>, we found that this rounding process allows cancer cells to travel more freely and spread around the body more easily. </p>
<p>To find out how Rac and Rho are involved in free radicals’ effects on cancer, we grew melanoma cells in the lab and treated them with a battery of antioxidants to remove the reactive oxygen species. As a result the cells became more rounded and moved faster, making them more likely to spread.</p>
<p>But if we used drugs to inhibit the Rho signals and boost the Rac, the amount of free radicals increased and the cells became longer and slower. We also saw that the increase in free radicals switched on certain genes in the cells, <a href="http://scienceblog.cancerresearchuk.org/2009/10/04/high-impact-science-p53/">such as p53</a>, which can protect us against cancer but disappears as cancers become more aggressive, and PIG3, which helps with <a href="http://scienceblog.cancerresearchuk.org/2015/09/18/expert-opinion-treating-cancer-by-exploiting-how-its-dna-is-repaired/">DNA repair</a>. Unexpectedly, we found that the PIG3 further suppressed Rho activity.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/98659/original/image-20151016-25146-9x89cd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/98659/original/image-20151016-25146-9x89cd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/98659/original/image-20151016-25146-9x89cd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/98659/original/image-20151016-25146-9x89cd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/98659/original/image-20151016-25146-9x89cd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/98659/original/image-20151016-25146-9x89cd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/98659/original/image-20151016-25146-9x89cd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Antioxidant overdose?</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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<p>We confirmed this by looking at mice with skin tumours. The animals were more likely to survive if the cancer cells had higher levels of PIG3, linked to the increase in free radicals. These tumours grew more slowly and cancer cells didn’t spread as much.</p>
<p>By contrast, we found that human patients that had low levels of PIG3 had cancer cells that were much more likely to be rounded and linked to faster travel around the body. At the same time, cancer patients’ <a href="http://cancergenome.nih.gov/">genetic records</a> showed us that individuals whose melanoma spread had low amounts of PIG3 but high levels of proteins controlled by Rho.</p>
<p>So in short, using drugs to reduce Rho and increase Rac produced an increase in free radicals and therefore PIG3, reducing the chances that the cancer cells would spread. This contrasts strongly with the idea that antioxidants, which reduce free radicals, can help treat the disease.</p>
<h2>Caution for antioxidants</h2>
<p>Most of our work was carried out in lab-grown melanoma cells, so there’s still more work to be done to show whether the drugs that inhibit Rho signals could stop melanoma spreading in patients. But the same drugs are being tested in clinical trials for other diseases, such as glaucoma, high blood pressure and heart disease, so we know they are safe to use in patients. Our research adds to the <a href="http://www.ncbi.nlm.nih.gov/pubmed/25840982">growing evidence</a> that indicates this family of drugs could work to slow down the spread of skin cancer. </p>
<p><a href="http://www.nejm.org/doi/full/10.1056/NEJM199404143301501">Other studies</a> indicate antioxidants can <a href="http://www.ncbi.nlm.nih.gov/pubmed/15572756">increase the risk</a> of cancer and <a href="http://www.ncbi.nlm.nih.gov/pubmed/24477002%5D">accelerate its progression</a>. High doses of antioxidants <a href="http://www.ncbi.nlm.nih.gov/pubmed/10442346">could also interfere</a> with some cancer treatments, such as chemotherapy, that rely on free radicals to damage and eventually kill the cancer cells. </p>
<p>While our results don’t prove that antioxidants are harmful for healthy cells, they sound an important note of caution about the use of antioxidants in patients that have already developed cancer. More work is needed to fully understand the benefits and drawbacks of taking antioxidant supplements. And we need to find a way to inhibit the “bad” free radicals and allow the “good” ones to do their work.</p><img src="https://counter.theconversation.com/content/49255/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Victoria Sanz-Moreno receives funding from Cancer Research UK. </span></em></p>New research suggests that far from helping treatment, antioxidants can change cancer cells to make them spread more quickly.Victoria Sanz-Moreno, Head of the Tumour Plasticity Lab, King's College LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/484612015-10-02T13:14:48Z2015-10-02T13:14:48ZNew research shows how to trap cancer by turning your body against the tumour<figure><img src="https://images.theconversation.com/files/96974/original/image-20151001-23105-1d8k0av.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-233501644/stock-photo-digital-illustration-of-lung-cancer-cells-in-color-background.html?src=GU99Ss-bABNBC2vA7zI2rQ-1-70">www.shutterstock.com</a></span></figcaption></figure><p>Cancer happens when cells in the body start growing uncontrollably. But what if the tissue surrounding a tumour could be enlisted to stop the cancer spreading? <a href="http://embor.embopress.org/content/16/10/1394">New research</a> gives the first evidence of how this might be possible by treating mice with a new drug that made cancer cells less likely to grow in other parts of the body.</p>
<p>Many cancer researchers believe that targeting the spread of cancer to other organs, otherwise known as metastasis, holds the key to successfully <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709494/">treating the disease</a> because metastasis is the cause of death for 90% of those who die of cancer.</p>
<p>In the past, many treatments aimed at preventing metastasis have been targeted at tumour cells themselves, for example with chemotherapy, which can have severe side effects. This approach can show some success but after a while the tumour cells can become resistant to the treatment and the cancer then spreads.</p>
<h2>Welcome environment</h2>
<p><a href="http://www.biomedcentral.com/1741-7015/13/45">Recent research</a> has also shown that the cells and proteins that surround a tumour play an important role in determining how it behaves. As a tumour develops, it sends out messages to surrounding cells, recruiting their help in creating a micro-environment with suitable conditions for the cancer to spread. These cells can then communicate with the tumour cells to encourage them to grow.</p>
<p>A large proportion of the cells found in the tumour micro-environment are cancer-associated <a href="http://medicalxpress.com/news/2015-09-scientists-cancer-cells.html">fibroblasts</a> (CAFs). In normal tissue, fibroblasts help to build the protein scaffolding or “matrix” that gives our organs their shape and helps heal wounds. However in cancer, fibroblasts are co-opted into re-sculpting and stiffening the surrounding matrix. This helps the tumour to grow larger by encouraging cells to divide and allows cancer cells to escape into the bloodstream from where they can then <a href="http://www.ncbi.nlm.nih.gov/pubmed/20822891">spread to other parts of the body</a>.</p>
<p>The new study, by researchers at the <a href="http://www.crick.ac.uk/research/">Francis Crick Institute</a> and published in EMBO Reports, found that when CAFs were grown in low-oxygen conditions they no longer attempted to change the structure of the surrounding scaffolding and started behaving more like normal fibroblasts again. The matrix remained flexible and, crucially, tumour cells were then unable to spread through it. The research provides the first clues of how we could target this process and help bring the cancer-associated fibroblast cells back on side against the cancer.</p>
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<img alt="" src="https://images.theconversation.com/files/96976/original/image-20151001-23101-157stlj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/96976/original/image-20151001-23101-157stlj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/96976/original/image-20151001-23101-157stlj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/96976/original/image-20151001-23101-157stlj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/96976/original/image-20151001-23101-157stlj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/96976/original/image-20151001-23101-157stlj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/96976/original/image-20151001-23101-157stlj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">This doesn’t look like cheese.</span>
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<p>Further experiments found that the CAFs’ change in behaviour was caused by a protein that is involved in sensing the amount of oxygen available to the cells. The team then used a drug in the mice with cancer that fools this oxygen sensor into behaving as if there is no oxygen present. They found that the cancer was then less likely to spread in those mice that had been treated with the drug than in those that hadn’t. </p>
<h2>Promising approach</h2>
<p>As the team involved in the study readily acknowledge, this approach is still very much in its infancy. However, it is an exciting development in the way we think about how cancer can be treated. One of the great challenges in cancer treatment is that tumour cells are genetically unstable and as a result can become <a href="http://www.cancerresearchuk.org/about-cancer/cancers-in-general/cancer-questions/why-isnt-my-treatment-working">resistant to chemotherapy</a>. CAFs and other cells are more stable and so will hopefully be less likely to develop resistance to emerging treatments if the findings of the research fulfil their promise.</p>
<p>As our understanding of the complex relationship between cancer and our bodies evolves, we will find new ways to target and combat the disease. It is very likely that the chemotherapies of the future will exploit these interactions, providing hope for better, more effective treatments.</p><img src="https://counter.theconversation.com/content/48461/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Allinson 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>Novel drugs that reduce the spread of cancer in mice could pave the way for changing the way we fight tumours.Sarah Allinson, Senior Lecturer, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/479062015-09-23T16:36:52Z2015-09-23T16:36:52ZStarving cancer cells of sugar could be the key to future treatment<figure><img src="https://images.theconversation.com/files/95882/original/image-20150923-2617-1frwddr.jpg?ixlib=rb-1.1.0&rect=0%2C1%2C736%2C547&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Is sugar the answer for tackling cancer cells?</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/5814247339/">Flickr/Wellcome Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>All the cells in our bodies are programmed to die. As they get older, our cells accumulate toxic molecules that make them sick. In response, they eventually break down, clearing the way for new, healthy cells to grow. This “<a href="http://www.ncbi.nlm.nih.gov/books/NBK26873/">programmed cell death</a>” is a natural and essential part of our wellbeing. Every day, billions of cells die like this in order for the whole organism to continue functioning as it is supposed to.</p>
<p>But as with any programme, errors can occur and injured cells that are supposed to die continue to grow and divide. These damaged cells can eventually become malignant and generate tumours. In order to <a href="http://www.ncbi.nlm.nih.gov/pubmed/19351640">avoid their programmed cell death</a> in this way, cancer cells reorganise their metabolism so they can cheat death and proliferate indefinitely.</p>
<p>Cancer researchers have <a href="http://www.ncbi.nlm.nih.gov/pubmed/19460998">known for decades</a> that tumours use a faster metabolism than normal cells in our body. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19029908">One classic example</a> of this is that cancer cells increase their consumption of glucose to fuel their rapid growth and strike against programmed cell death. This means that limiting glucose consumption in cancer cells is becoming an <a href="http://www.ncbi.nlm.nih.gov/pubmed/16892078">attractive tool</a> for cancer treatments.</p>
<h2>A new hope?</h2>
<p>You may have seen <a href="http://www.dailymail.co.uk/home/you/article-1025497/The-anti-cancer-diet--introducing-healthy-new-way-life.html">articles</a> or <a href="http://www.canceractive.com/cancer-active-page-link.aspx?n=3087">websites advocating</a> that starving patients of sugar is crucial for getting rid of tumours or that eating less sugar reduces the risk of cancer. The story is not that simple. Cancer cells always <a href="http://www.ncbi.nlm.nih.gov/pubmed/23177934">find alternatives</a> to fuel their tank of glucose, no matter how little sugar we ingest. There is not a direct connection between eating sugar and getting cancer and it is always advisable to talk to your doctor if you have doubt about your diet. </p>
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<span class="caption">Chemotherapy – the most common cancer treatment.</span>
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<p>Researchers <a href="http://www.ncbi.nlm.nih.gov/pubmed/19270154">have demonstrated</a> that cancer cells use glucose to generate the building blocks of the cellular compounds needed for rapid tumour growth. They also use it to <a href="http://www.ncbi.nlm.nih.gov/pubmed/19029908">generate molecules</a> that guard against the toxic accumulation of reactive oxygen species, the cell-damaging molecules that activate programmed cell death. This means that glucose serves as a master protector against cell death.</p>
<p>If the amount of sugar we eat doesn’t affect this process, the question we need to answer is how the cancer cells are instructed to consume more glucose. Who is filling the fuel tank? We have discovered that what allows tumours to evade their natural cause of death in this way is a protein that is overproduced in virtually every human cancer but not in normal cells.</p>
<h2>Turbocharged growth</h2>
<p>In a <a href="http://www.nature.com/ncomms/2015/150810/ncomms8882/full/ncomms8882.html">recent study</a> published in Nature Communications we showed that cancer cells stimulate the over-production of the protein known as PARP14, enabling them to use glucose to turbocharge their growth and override the natural check of cell death. Using a combination of genetic and molecular biology approaches, we have also demonstrated that inhibiting or reducing levels of PARP14 in cancer cells starves them to death.</p>
<p>The best news is that by comparing cancer tissues (biopsies) from patients that has survived cancer and those that have died, we have found that levels of PARP14 were significantly higher in those patients that have died. This means that levels of PARP14 in cancer tissues could also predict how aggressive the cancer would be and what the chances are of a patient’s survival.</p>
<p>This means that a treatment which could block the protein could represent a significant revolution in the future of cancer treatment. What’s more, unlike traditional chemotherapy and radiotherapy, the use of PARP14 inhibitors would only kill cancer cells and not healthy ones. The next step is to design and generate new drugs that can block this protein and work out how to use them safely in patients.</p><img src="https://counter.theconversation.com/content/47906/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Concetta Bubici receives funding from Key Kendall Leukaemia Fund. </span></em></p><p class="fine-print"><em><span>Salvatore Papa receives funding from Foundation for Liver Research and AMMF-Cholangiocarcinoma Charity</span></em></p>Eating less sugar isn’t enough to stop glucose-hungry cancer cells but new research points the way to how we might starve them to death.Concetta Bubici, Lecturer in biomedical science, Brunel University LondonSalvatore Papa, Senior scientist, Institute of Hepatology, Birkbeck, University of LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/314432014-09-10T05:29:56Z2014-09-10T05:29:56ZObesity takes patients one step closer to liver cancer<figure><img src="https://images.theconversation.com/files/58601/original/gvyfgwsz-1410279508.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Too much fat is not good.</span> <span class="attribution"><a class="source" href="http://en.wikipedia.org/wiki/File:Fatmouse.jpg">Human Genome wall for SC99</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Liver cancer is one of the most deadly diseases in the world with around 700,000 patients being diagnosed and more than 600,000 patients dying of the disease annually, according to the <a href="http://www.cancer.org/cancer/livercancer/detailedguide/liver-cancer-what-is-key-statistics">American Cancer Society</a>. It is more common in the sub-Saharan and southeast-Asian countries, where hepatitis and alcohol abuse are the main causes. These two factors trigger liver cirrhosis, leading to cancer.</p>
<p>The deadly disease is now spreading to rich countries. What is particularly disturbing in there is that about 40% of the patients get liver cancer without viral infection or symptoms of alcohol abuse. But they were obese and had an intense form of fatty liver disease called non-alcoholic steatohepatitis, or NASH.</p>
<p>However, obesity alone cannot explain the cause of liver cancer. If it was the only risk factor, there would have been a lot more instances of liver cancer in obese patients than normal patients. But that wasn’t the case. </p>
<p>Michael Karin, professor of pharmacology, University of California at San Diego wanted to find out the exact link. In an experiment with mice, he noticed that obese mice eating a diet rich in fat did not suddenly develop liver cancer. Yet, these obese mice had a higher risk of liver cancer if they were exposed to some sort of cancer causing agent such as a chemical called diethylnitrosamine. He started looking for a naturally occurring risk factor that could tilt the balance from mere liver damage to liver cancer.</p>
<p>Karin suspected that a phenomenon called endoplasmic reticulum (ER) stress may have a role to play. ER stress happens whenever the cells of the liver have to work extra hard to produce more proteins. After the proteins are made, they are neatly shaped into their proper form. If there are too many proteins being made at the same time, the cell doesn’t have enough machinery available to package the proteins and it goes then into panic mode, known as ER stress.</p>
<p>Conditions such as hepatitis, diabetes or even long-term obesity in the patient can cause ER stress. Karin wanted to confirm whether ER stress pushed obese mice first towards intense fatty liver state, or NASH, and then ultimately towards liver disease.</p>
<p>Karin used a mutant strain of mice whose liver cells could artificially be made to temporarily undergo ER stress. The liver cells of these mutant mice produce an enzyme called urokinase plasminogen activator that causes ER stress. The enzyme stays within the cells for some time and then gets degraded, relieving ER stress. So the mice are completely healthy with no liver problems.</p>
<p>But Karin found that when the ER-stressed mice were fed a diet rich in fat, unlike the normal mice that simply turned obese, these mice started accumulating a lot of fat in their livers. Instead of temporary ER stress, the liver cells of these mice showed persistent signs of ER stress throughout their life, undergoing slow damage and death, eventually leading to liver tumours. Their results have been published in the journal <a href="http://dx.doi.org/10.1016/j.ccr.2014.07.001">Cancer Cell</a>.</p>
<p>However, it is not all bad news. Karin noticed that if he could stop the process whereby ER stress causes inflammation and damage in the livers, the tumours stopped growing. He achieved this by blocking signalling molecules of the TNF pathway. The molecules of this pathway attract white blood cells called macrophages into the liver, causing inflammation. </p>
<p>On blocking signalling through the TNF pathway, he noticed that the liver stored less fats, making the mice look healthier. Karin thinks that drugs blocking this pathway, along with surgery and chemotherapy could be the answer to keep liver cancer under check in obese patients.</p><img src="https://counter.theconversation.com/content/31443/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>Liver cancer is one of the most deadly diseases in the world with around 700,000 patients being diagnosed and more than 600,000 patients dying of the disease annually, according to the American Cancer…Anwesha Ghosh, PhD student in Biology, University of RochesterLicensed as Creative Commons – attribution, no derivatives.