Cancer cells hibernate to survive chemotherapy, finds study
Researchers discover that cancer cells go into hibernation to avoid chemotherapy effects.
12 January, 2021
Credit: Adobe Stock
- Cancer cells go into a state similar to hibernation when attacked by chemotherapy.
- The low-energy state is similar to diapause—the embryonic survival strategy of over a 100 species of mammals.
- Researchers hope to use these findings to develop new cancer-fighting therapies.
<p>When attacked by chemotherapy, all cancer cells have the ability to start hibernating in order to wait out the threat, finds new research. The cancer cells hijack an evolutionary survival mechanism to transition into a state of "rest" until chemotherapy stops. Devising therapies to target the cells in this slow-dividing state can prevent the cancer from regrowing.</p><p>The discovery was made by Dr. Catherine O'Brien and the team from the Princess Margaret Cancer Centre in Canada. Professor O'Brien, who teaches in the Department of Surgery at the University of Toronto, <a href="https://www.uhn.ca/corporate/News/PressReleases/Pages/Cancer_cells_hibernate_like_bears_to_evade_harsh_chemotherapy.aspx" target="_blank">described</a> that the tumor acts "like a whole organism, able to go into a slow-dividing state, conserving energy to help it survive."</p>
<p>She compared this to animals who enter hibernation to get through difficult environmental conditions. Dr. Aaron Schimmer, Director of the Research Institute and Senior Scientist at the Princess Margaret, was even more specific, sharing that the behavior of the cells was akin to that of "bears in winter."</p><p style="margin-left: 20px;">"We never actually knew that cancer cells were like hibernating bears," <a href="https://www.uhn.ca/corporate/News/PressReleases/Pages/Cancer_cells_hibernate_like_bears_to_evade_harsh_chemotherapy.aspx" target="_blank">explained</a> Schimmer. "This study also tells us how to target these sleeping bears so they don't hibernate and wake up to come back later, unexpectedly."</p><p>He thinks this adaptation by the cells can be the key cause of resistance to drugs.</p>
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTQ0NDU2Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzODM0NjgzNn0.1fPKPtlY0t1_HZsxaMh4N0rYwX3Zwtk0giTiQ_Pivrg/img.jpg?width=980" id="5bdcc" class="rm-shortcode" data-rm-shortcode-id="a95ad1231faa765e2d1fdbbbee294243" data-rm-shortcode-name="rebelmouse-image" data-width="696" data-height="696" />
Cancer cells may go to into diapause, entering a drug-tolerant persister (DTP) state.
Credit: Cell
<p>The scientists arrived at their observations by observing human colorectal cancer cells, which were treated with chemotherapy in a petri dish. This caused the cells to go into a slow-dividing state during which they ceased expanding and needed little nutrition. Such a reaction continued as long as chemotherapy was present.</p><p>The low-energy state of the cells was similar to <strong>diapause</strong>—the embryonic survival strategy of over a 100 species of mammals. They protect embryos by keeping them inside their bodies during extreme situations of very high or very low temperatures, or when sustenance is not available. Minimal cell division takes place when animals are in this state, while their metabolism slows to a crawl. </p><p style="margin-left: 20px;">"The cancer cells are able to hijack this evolutionarily conserved survival strategy, even as it seems to be lost to humans," <a href="https://www.uhn.ca/corporate/News/PressReleases/Pages/Cancer_cells_hibernate_like_bears_to_evade_harsh_chemotherapy.aspx" target="_blank">pointed out</a> Dr. O'Brien. </p>
<p>When the cells are in this state, they activate a cellular process known as <em>autophagy</em> (means "self-devouring"). While this is taking place, and if no other nutrients are present, the cell feeds on its own proteins and other cellular parts to survive. Observing that, the scientists tried impeding autophagy and found that the cancer cells were destroyed, succumbing to chemotherapy. Knowing this can lead to new therapies, according to O'Brien, who <a href="https://www.uhn.ca/corporate/News/PressReleases/Pages/Cancer_cells_hibernate_like_bears_to_evade_harsh_chemotherapy.aspx" target="_blank">proposed</a> that "We need to target cancer cells while they are in this slow-cycling, vulnerable state before they acquire the genetic mutations that drive drug-resistance."</p><p>Check out the new study <a href="http://dx.doi.org/10.1016/j.cell.2020.11.018" target="_blank">published in Cell.</a></p>
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Michio Kaku: 3 mind-blowing predictions about the future
What lies in store for humanity? Theoretical physicist Michio Kaku explains how different life will be for your ancestors—and maybe your future self, if the timing works out.
04 January, 2021
- Carl Sagan believed humanity needed to become a multi-planet species as an insurance policy against the next huge catastrophe on Earth. Now, Elon Musk is working to see that mission through, starting with a colony of a million humans on Mars. Where will our species go next?
- Theoretical physicist Michio Kaku looks decades into the future and makes three bold predictions about human space travel, the potential of 'brain net', and our coming victory over cancer.
- "[I]n the future, the word 'tumor' will disappear from the English language," says Kaku. "We will have years of warning that there is a colony of cancer cells growing in our body. And our descendants will wonder: How could we fear cancer so much?"
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Scientists stumble across new organs in the human head
New cancer-scanning technology reveals a previously unknown detail of human anatomy.
20 October, 2020
Credit: Valstar et al., Netherlands Cancer Institute
- Scientists using new scanning technology and hunting for prostate tumors get a surprise.
- Behind the nasopharynx is a set of salivary glands that no one knew about.
- Finding the glands may allow for more complication-free radiation therapies.
<p>The research began about as far away from where it ended up as possible. Doctors were using PSMA PET/CT scans to assess whether patients' prostate cancer had spread to other parts of their bodies. In addition to being a promising new technology for detecting tumors, PSMA PET/CT scans also happen to be good at imaging salivary glands. Still, radiation oncologist Wouter Vogel and oral and maxillofacial surgeon Matthijs Valstar didn't know quite what to make of two lit-up areas behind the <a href="https://www.healthline.com/health/human-body-maps/nasopharynx#1" target="_blank">nasopharynx</a> that looked an awful lot like big, undiscovered salivary glands.</p><p>Since finding a whole new organ in the human body at this point is unexpected, to say the least, the researchers re-examined the PSMA PET/CT from all 100 patients in their study, plus two cadavers. Every one of them had the same thing. </p><p><a href="https://www.nki.nl/topmenu/about-the-nki/news/cancer-researchers-discover-new-salivary-gland/" target="_blank">Says senior author of the study Vogel</a>, "As far as we knew, the only salivary or mucous glands in the nasopharynx are microscopically small, and up to 1000 are evenly spread out throughout the mucosa. So, imagine our surprise when we found these."</p><p>The study's lead author Valstar adds, "The two new areas that lit up turned out to have other characteristics of salivary glands as well."</p><p>Vogel and Valstar work for the <a href="https://www.nki.nl" target="_blank" rel="noopener noreferrer" style="">Netherlands Cancer Institute</a>, specializing in the effects of radiation therapy on the head and neck. Their discovery may help technicians alleviate some common radiation side effects now that they know to avoid the new salivary organs, which they've named the "tubarial salivary glands."</p><p>The research is published in <a href="https://www.sciencedirect.com/science/article/pii/S0167814020308094" target="_blank">Radiotherapy & Oncology</a>.</p>
PSMA PET/CT technology
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="676e611b970c9b516cace0870447b325"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/RHAyoQF09X4?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>PSMA PET/CT is a new combination of <a href="https://www.mayoclinic.org/tests-procedures/pet-scan/about/pac-20385078" target="_blank">PET scans</a> and <a href="https://www.mayoclinic.org/tests-procedures/ct-scan/about/pac-20393675" target="_blank">CT scans</a> that is believed to offer a more reliable means of locating prostate cancer metastasis. A <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2020/prostate-cancer-psma-pet-ct-metastasis" target="_blank" rel="noopener noreferrer">study</a> published last spring suggests it may be the most accurate way to diagnose prostate cancer metastasis than any method previously available.</p><p>Prior to PSMA PET/CT, the primary way to look for metastatic prostate cancer was to image the body using x-ray-based CT scans and to perform bone scans, since bone is where prostate cancer often spreads. CT scans, however, often miss small tumors, and bone scans can generate false positives as a result of other damage or abnormalities that have nothing to do with prostate cancer.</p><p>PSMA PET/CT scans track the travels of an intravenously administered radioactive glucose tracer throughout the body. For hunting down prostate cancer, this tracer contains a molecule that binds to the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472940/" target="_blank">PSMA</a> protein that's present in large amounts in prostate tumors. The molecule is linked to a radioisotope, <a href="https://netrf.org/2018/11/13/gallium-68-scan-for-neuroendocrine-tumors/" target="_blank" rel="noopener noreferrer">gallium-68</a> (Ga-68).</p><p>In last spring's research, PSAM PET/CT was shown to be 27 percent more accurate than previous methods at finding metastases (92 percent accuracy as opposed to 65 percent). In addition, it was found to be much less likely to produce false positives, and it was particularly good at detecting tumors far removed from the prostate.</p>A good kind of avoidance behavior
<p>"Radiation therapy can damage the salivary glands," says Vogel, "which may lead to complications. Patients may have trouble eating, swallowing, or speaking, which can be a real burden."</p><p>The researchers looked back through the cases of 723 patients who had undergone radiation treatment, interested in seeing if inadvertent radiation of the tubarial glands was associated with the complications experienced by the patients. It turned out that this <em>was</em> the case: In cases where more radiation had been delivered to this area, patients did indeed report more in the way of complications of the type one would expect when salivary glands are radiated.</p><p>Now that we know the tubarial salivary glands exist, therapists can stay out of their way. Vogel says, "For most patients, it should technically be possible to avoid delivering radiation to this newly discovered location of the salivary gland system in the same way we try to spare known glands."</p><p>He's hopeful that that things may be about to get at least a bit better for cancer patients: "Our next step is to find out how we can best spare these new glands and in which patients. If we can do this, patients may experience less side effects which will benefit their overall quality of life after treatment."</p>
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Study calls out the genes that make cancer cells so hard to kill
Researchers from the University of Toronto published a new map of cancer cells' genetic defenses against treatment.
24 September, 2020
Credit: CI Photos/Shutterstock
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<p>There's a great diversity among cancer cells, though many of them share one unfortunate trait: They're often quite adept at resisting the body's immune system. The immune system's T killer cells can theoretically take out cancer cells, and immunotherapies enhance existing T cells' potency. Still, cancer cells are often impervious to them, can mutate to evade them, and worst of all, can acquire "cancer resistance mutations" that cause the disease to worsen in response to T cells. This is especially true of the cells in solid tumors.</p><p>A study from researchers at University of Toronto catalogs the genes in cancer tumors that allow the disease to so effectively resist immunotherapy. Its authors hope that their findings will eventually lead to the development of more successful cancer treatments.</p><p>The study is published in the journal <a href="https://www.nature.com/articles/s41586-020-2746-2" target="_blank">Nature</a>.</p>
A moving target
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQzNjQ2Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1MDM3OTA0N30.z4u2eaulqRu8cslqqny8t9G7iaHr_DarbDJSFKLdDwI/img.jpg?width=980" id="21b22" class="rm-shortcode" data-rm-shortcode-id="aefbbccdf3bb0d25bf14268ab87a821f" data-rm-shortcode-name="rebelmouse-image" alt="IV drip" data-width="1440" data-height="960" />Credit: Marcelo Leal/Unsplash
<p>Speaking to <a href="https://www.utoronto.ca/news/u-t-researchers-identify-genes-enable-cancer-evade-immune-system" target="_blank" rel="noopener noreferrer">U of T News</a>, lead author of the study molecular geneticist <a href="http://www.moleculargenetics.utoronto.ca/faculty/2014/9/30/jason-moffat" target="_blank" rel="noopener noreferrer">Jason Moffat</a> of the university's <a href="https://ccbr.utoronto.ca/donnelly-centre-cellular-and-biomolecular-research" target="_blank" rel="noopener noreferrer">Donnelly Centre for Cellular and Biomolecular Research</a> says, "Over the last decade, different forms of immunotherapy have emerged as really potent cancer treatments, but the reality is that they only generate durable responses in a fraction of patients and not for all tumor types."</p><p>There can be a significant degree of heterogeneity between cancer cells from human to human, and even within the same person, making the development of therapies maddeningly difficult. Attempting to address potential cancer-cell vulnerabilities across these variations is a life-or-death game of whack-a-mole.</p><p>"It's an ongoing battle between the immune system and cancer, where the immune system is trying to find and kill the cancer whereas the cancer's job is to evade that killing," says Moffat.</p>Mapping the mechanisms
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQzNjQ3Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyMjQ1OTM0MX0.HNtivrlU9VBYxcG9JaWKvPJ5RrBsgqd8Fw6ohfSpfh0/img.jpg?width=980" id="0faa6" class="rm-shortcode" data-rm-shortcode-id="7687cdc5abe93503764c1c0401b65fd4" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="810" />Illustration: genes (red, green, and blue spots within the nuclei of HeLa cells) artificially superimposed on images of multi-well plates.
Credit: National Cancer Institute/Unsplash
<p>Moffat and his colleagues decided to investigate and identify genes within cancer cells that help them defeat treatment. Co-lead author Keith Lawson of Moffat's lab explains that "it's important to not just find genes that can regulate immune evasion in one model of cancer, but what you really want are to find those genes that you can manipulate in cancer cells across many models because those are going to make the best therapeutic targets."</p><p>To accomplish this, the researchers, working with scientists at <a href="https://www.agios.com" target="_blank">Agios Pharmaceuticals</a> in Cambridge, Massachusetts, first exposed cells from breast, colon, kidney and skin cancer tumors to T cells in lab dishes. This established a baseline of their responses to treatment. Next, using CRISPR, the scientists went through the cells, exhaustively turning off one gene at a time to determine its role in immunotherapy resistance by comparing the cells' response to the T cells compared to their original baseline response.</p><p>The team identified 182 "core cancer intrinsic immune evasion genes" that affected the cells' response to T cells. The fact that some of the identified genes were already known to be involved in resistance provided the researchers with some confidence that they were on the right track.</p><p>Still, many of the genes they ID'ed had not been previously implicated. "That was really exciting to see because it means that our dataset was very rich in new biological information," says Lawson.</p>It's complicated
<p>Unfortunately, Moffat's research also makes clear that defeating cancer-cell resistance is not as simple as removing certain genes. It's true that when the team switched off some of the genes they'd identified, the cancer cells became more vulnerable to T cells, but on the other hand, removal of some other genes made the cancer cells more resistant.</p><p>There also appear to be relationships between multiple genes that complicate matters. </p><p>The team explored the manipulation of the genes that allow cancer cells to engage in <a href="https://en.wikipedia.org/wiki/Autophagy" target="_blank">autophagy</a>, the process by which cells clear out no-longer useful materials to facilitate speedy recovery from damage. Surprisingly, when the researchers deleted certain genes responsible for cancer cells' autophagy, they found the cells' resistance to T cells increased. Apparently, removing one autophagy gene strengthened another mutated autophagy gene.</p><p>"We found this complete inversion of gene dependency," said Moffat. "We did not anticipate this at all. What it shows us is that genetic context — what mutations are present — very much dictates whether the introduction of the second mutation will cause no effect, resistance or sensitivity to therapy."</p><p>There remains a long road ahead when it comes to unraveling cancer cells' resistance to immunotherapy. However, this new study presents a new map that can help scientists navigate what comes next.</p>
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Study links 'sun-seeking behavior' to genes involved in addiction
A large-scale study from King's College London explores the link between genetics and sun-seeking behaviors.
18 September, 2020
Credit: Grisha Bruev on Shutterstock
- There are a number of physical and mental health benefits to sun exposure, such as boosted vitamin D and serotonin levels and stronger bones.
- Addictions are multi-step conditions that, by definition, require exposure to the addictive agent and have also been proven to have a genetic factor. Countless people are exposed to addictive things, but not all become addicted. This is because of the genetic component of addiction.
- This large-scale study explores the link between sun-seeking behaviors and the genetic markers for addiction.
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The benefits of sunlight
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQyMjI1Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNzk0NDUxNH0.lbYbZidJkNXPUcWM6m8cucuzAFOANkqPaIVfJdqkJ4Q/img.jpg?width=1245&coordinates=0%2C52%2C0%2C52&height=700" id="d5fcd" class="rm-shortcode" data-rm-shortcode-id="f44fcc9a31393c8102803eb50d01a19a" data-rm-shortcode-name="rebelmouse-image" alt="woman sitting on dock in the sunlight" data-width="1245" data-height="700" />The mental and physical health benefits of sunlight have been heavily researched.
Credit: eldar nurkovic on Shutterstock
<p>The benefits of sunlight have been widely discussed for many years. In fact, there are a number of physical and mental health benefits to sun exposure.</p><p><strong>Sunshine (and the lack of) impacts your hormone levels. </strong></p><p>Sunlight (and alternatively, the lack of sunlight) triggers the release of certain hormones in your brain. Exposure to sunlight is thought to increase serotonin, which is associated with boosting your mood and helping you feel calm and focused. </p><p>Alternatively, dark lighting triggers melatonin, a hormone that is helpful in allowing you to rest and fall asleep. Without enough sunlight, your serotonin levels can dip - and low serotonin levels have been associated with a higher risk of major depression with seasonal pattern (formerly known as seasonal affective disorder).</p><p><strong>Sunlight can build strong bones. </strong></p><p>Exposure to the ultraviolet-B radiation in the sun's rays can interact with your skin, causing it to create vitamin D. <a href="https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-d/" target="_blank" rel="noopener noreferrer">According to NHS</a>, vitamin D helps regulate the amount of calcium and phosphate in the body. A lack of vitamin D can lead to bone deformities or bone pain. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2290997/" target="_blank" rel="noopener noreferrer">A 2008 study</a> has shown that even 30 minutes in sunlight (while wearing a bathing suit) can boost vitamin D levels. </p><p><strong>Can sunlight actually prevent cancer? </strong></p><p>Although heavy exposure to sunlight has been proven to contribute to certain skin cancers, a moderate amount of sunlight has actually been shown to have preventative benefits.</p><p><a href="https://cjasn.asnjournals.org/content/3/5/1548.full" target="_blank" rel="noopener noreferrer">According to a 2008 study</a> from the Clinical Journal of the American Society of Nephrology, those who live in areas with fewer daylight hours are more likely to have some specific cancers (including but not limited to colon cancer, ovarian cancer, and prostate cancer) than those who live in areas with increased daylight hours.</p><p><strong>Additionally, sunlight has been shown to help people with skin conditions such as psoriasis. </strong></p><p><a href="http://www.who.int/uv/faq/uvhealtfac/en/index1.html" target="_blank" rel="noopener noreferrer">According to the World Health Organization</a>, sun exposure may also be able to help treat skin conditions such as psoriasis, eczema, jaundice, and acne. <a href="https://www.healthline.com/health/depression/benefits-sunlight#benefits" target="_blank" rel="noopener noreferrer">Some research</a> has also indicated the sun benefits people who struggle with rheumatoid arthritis (RA), systemic lupus erythematosus, and inflammatory bowel disease. </p>Can you be addicted to the sun?
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQyMjI1Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY2NjI2NzMwOX0.rB2IFcqqFIwqCn1TF-Upv9_O3KlmI_H4MtYx6L7bTqI/img.jpg?width=1245&coordinates=31%2C0%2C31%2C0&height=700" id="c5925" class="rm-shortcode" data-rm-shortcode-id="384e08fdcd535ed2b792eef419af9e2c" data-rm-shortcode-name="rebelmouse-image" alt="hands holding up the sun" data-width="1245" data-height="700" />The large-scale study examines the link between addiction and sunlight, with some surprising results...
Credit: KieferPix on Shutterstock
<p>Addictions are multi-step conditions that, by definition, require exposure to the addictive agent. Due to the increase of serotonin (a chemical in the human body <a href="https://www.healthline.com/health/mental-health/serotonin" target="_blank">that has been proven</a> to help reduce depression, regulate anxiety, and maintain bone health), it's natural that being exposed to prolonged periods of sunlight could become somewhat addictive to the human body and mind. We crave things that make us feel good, and sometimes those cravings become something we depend on. This is the very nature of addiction.</p><p>Countless people are exposed to addictive things (substances, medications, and yes, even the sun), but not all become addicted. This is because of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506170/" target="_blank" rel="noopener noreferrer">genetic component of addiction</a>. </p><p>A large-scale study from King's College in London examines more than 260,000 people to better understand how sun-seeking behavior in humans can be linked to genes involving addiction, behavior traits, and brain function. </p><p><strong>The study included two phases:</strong></p><p>Phase one suggested genetics play a role in sun-seeking behaviors and phase 2 helped pinpoint what those genetic markers are.</p><p>Phase 1: The researchers studied the detailed health information of 2,500 twins, including their sun-seeking behavior and their genetics. Identical twins in a pair were more likely to have similar sun-seeking behavior than non-identical twins, indicating that genetics plays a role here. </p><p>Phase 2: The team of researchers then were able to identify five key gene markers involved in this sun-seeking behavior from further analysis of 260,000 participants. Some of the genes indicated have been linked to behaviors traits that are associated with risk-taking and addiction (including smoking and alcohol consumption).</p><p><strong>What does this study really prove? </strong></p><p>Some may think it's natural to become addicted to something that makes you feel good. The physical and mental health benefits of the outdoors have been heavily studied...so what does this study really mean? </p><p>First and foremost, it means more research needs to be done to examine the link between human conditions and exposure to sunlight. Senior author Dr. Mario Falchi explains to the <a href="https://www.kcl.ac.uk/news/addicted-to-the-sun-its-in-your-genes" target="_blank">King's College London News Center</a>: "Our results suggest that tackling excessive sun exposure or use of tanning beds might be more challenging than expected, as it is influenced by genetic factors. It is important for the public to be aware of this predisposition, as it could make people more mindful of their behavior and the potential harms of excessive sun exposure."</p><p>Additionally, it could mean alternative treatments, and further research needs to be conducted in terms of how we treat certain conditions that are caused or heavily influenced by human exposure to sunlight. </p>
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