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Scientists have made a groundbreaking discovery in cancer research that could potentially transform the way we approach treatment. Researchers have identified certain pieces of DNA that act like “Bond villains” in the way they help cancers spread, and also contribute to tumors gaining resistance to anti-cancer drugs. These bits of genetic material are called extrachromosomal DNA, or ecDNA.
EcDNA is made up of small loops of DNA that exist outside the chromosomes, which are our cells’ primary repositories of genetic material. Chromosomes direct the growth of our bodies and determine our individual characteristics, while ecDNA acts like cancer-causing genes that have somehow separated themselves from a person’s chromosomes and have started to behave in ways that circumvent the normal rules of genetics. These little loops of DNA cause significant biological harm and are responsible for a large number of the most aggressive and serious cancers affecting people today.
The discovery of how ecDNA behaves inside our bodies is a significant game-changer in cancer research. Professor Paul Mischel of California’s Stanford University, one of the leaders of the program, says, “If we can block their activities, we can block the spread of these cancers.” The breakthrough is part of a major initiative known as the Cancer Grand Challenges, backed by Cancer Research UK and the US National Cancer Institute. This initiative funds multidisciplinary research programs that could develop novel routes for tackling cancer. In this case, it has provided £20m to fund the work on ecDNA’s involvement in cancers, and teams of chemists, biologists, geneticists, mathematicians, and immunologists based in California, London, and other centers are collaborating to show how these little loops of DNA cause such biological harm.
Scientists have shown in recent years that tumours occur because normal genes in a cell go wrong and cause that cell to divide uncontrollably, resulting in a tumour. These genes are known as oncogenes and can be targeted by a range of drugs and therapies. However, resistance to those drugs or therapies often appears after a while, allowing the cancer to return. The researchers have now discovered that in some of the most aggressive forms of cancer, the oncogenes aren’t where we thought they were. They are actually on extrachromosomal DNA.
EcDNA is not just a villain; it is a criminal mastermind. It can almost completely disappear from a tumour and then come back after you stop drug treatments, providing almost infinite adaptability. Nevertheless, scientists are confident that they will be able to find ways of removing ecDNA from patients. “It should be noted that ecDNA is a feature of cancer and not healthy tissue, so that raises hopes that when we find ways to remove it – through drugs or some form of therapy – then it will not have unpleasant side-effects,” said Dr. Mariam Jamal-Hanjani of University College London Cancer Institute.
The crucial point is that once we have found the cause of the problem, then it becomes possible to develop and try out all sorts of drugs and therapies to tackle that. “We are now looking to pinpoint the Achilles heel of ecDNA and have identified a protein that helps hold it together. We have also discovered a drug that has a promising effect on this protein. And in the coming years, we will test a lot more until we find the best one to tackle ecDNA and halt its pro-cancerous activities. It will take time, but I am confident we will get there,” said Howard Chang, a geneticist at Stanford University.