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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.

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.
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.
The study is published in the journal Nature.
A moving target
Credit: Marcelo Leal/Unsplash
Speaking to U of T News, lead author of the study molecular geneticist Jason Moffat of the university's Donnelly Centre for Cellular and Biomolecular Research 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."
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.
"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.
Mapping the mechanisms
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
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."
To accomplish this, the researchers, working with scientists at Agios Pharmaceuticals 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.
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.
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.
It's complicated
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.
There also appear to be relationships between multiple genes that complicate matters.
The team explored the manipulation of the genes that allow cancer cells to engage in autophagy, 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.
"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."
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.
- Will we win the battle against cancer? - Big Think ›
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- "Targeted Therapy Cocktail" Could Control, Perhaps Cure, Cancer ... ›
What early US presidents looked like, according to AI-generated images
"Deepfakes" and "cheap fakes" are becoming strikingly convincing — even ones generated on freely available apps.
Abraham Lincoln, George Washington
- A writer named Magdalene Visaggio recently used FaceApp and Airbrush to generate convincing portraits of early U.S. presidents.
- "Deepfake" technology has improved drastically in recent years, and some countries are already experiencing how it can weaponized for political purposes.
- It's currently unknown whether it'll be possible to develop technology that can quickly and accurately determine whether a given video is real or fake.
The future of deepfakes
<p>In 2018, Gabon's president Ali Bongo had been out of the country for months receiving medical treatment. After Bongo hadn't been seen in public for months, rumors began swirling about his condition. Some suggested Bongo might even be dead. In response, Bongo's administration released a video that seemed to show the president addressing the nation.</p><p>But the <a href="https://www.facebook.com/watch/?v=324528215059254" target="_blank">video</a> is strange, appearing choppy and blurry in parts. After political opponents declared the video to be a deepfake, Gabon's military attempted an unsuccessful coup. What's striking about the story is that, to this day, experts in the field of deepfakes can't conclusively verify whether the video was real. </p><p>The uncertainty and confusion generated by deepfakes poses a "global problem," according to a <a href="https://www.brookings.edu/research/is-seeing-still-believing-the-deepfake-challenge-to-truth-in-politics/#cancel" target="_blank">2020 report from The Brookings Institution</a>. In 2018, the U.S. Department of Defense released some of the first tools able to successfully detect deepfake videos. The problem, however, is that deepfake technology keeps improving, meaning forensic approaches may forever be one step behind the most sophisticated forms of deepfakes. </p><p>As the 2020 report noted, even if the private sector or governments create technology to identify deepfakes, they will:</p><p style="margin-left: 20px;">"...operate more slowly than the generation of these fakes, allowing false representations to dominate the media landscape for days or even weeks. "A lie can go halfway around the world before the truth can get its shoes on," warns David Doermann, the director of the Artificial Intelligence Institute at the University of Buffalo. And if defensive methods yield results short of certainty, as many will, technology companies will be hesitant to label the likely misrepresentations as fakes."</p>The COVID-19 pandemic has introduced a number of new behaviours into daily routines, like physical distancing, mask-wearing and hand sanitizing. Meanwhile, many old behaviours such as attending events, eating out and seeing friends have been put on hold.
VR experiments manipulate how people feel about coffee
A new study looks at how images of coffee's origins affect the perception of its premiumness and quality.
Expert drinking coffee while wearing a VR headset.
- Images can affect how people perceive the quality of a product.
- In a new study, researchers show using virtual reality that images of farms positively influence the subjects' experience of coffee.
- The results provide insights on the psychology and power of marketing.
Is empathy always good?
Research has shown how important empathy is to relationships, but there are limits to its power.
