A groundbreaking study led by U.S. and U.K. scientists offers new hope for tackling some of the most aggressive cancers by targeting rogue DNA fragments that allow tumors to grow and resist treatment. Published in Nature, the research shows that many hard-to-treat cancers contain circular pieces of extrachromosomal DNA (ecDNA), which fuel tumor survival and resistance to chemotherapy.
Researchers examined 39 types of tumors from nearly 15,000 patients in the U.K. and found that over 17% of the cancers studied contained ecDNA, particularly in aggressive breast, brain, and lung cancers. These rogue DNA loops, sitting outside the main chromosomes, carry genes that promote cancer growth and suppress immune response, making tumors more difficult to treat with conventional therapies.
“This is an important discovery because it affects patients who are really suffering due to the aggressive nature of their cancers,” said Dr. Paul Mischel, a pathology professor at Stanford University and senior author on the study. Mischel noted that ecDNA helps tumors rapidly develop genetic diversity, allowing them to adapt and resist anti-cancer drugs more effectively.
The study, funded by Cancer Grand Challenges (an initiative co-founded by Cancer Research UK and the U.S. National Cancer Institute), suggests a promising new approach: targeting ecDNA with drugs called CHK1 inhibitors, which can selectively destroy cancer cells containing ecDNA. Early trials on a CHK1 inhibitor, developed by Boundless Bio—a company co-founded by Mischel—showed success in reducing tumor growth and preventing resistance in mice when combined with traditional cancer treatments.
“This is not just a discovery about what makes cancer so aggressive; it points to a new class of therapies,” Mischel added. “This type of DNA is unique and creates distinct vulnerabilities that we can exploit.”
David Scott, director of Cancer Grand Challenges at Cancer Research UK, echoed the importance of targeting ecDNA, noting that ecDNA allows some of the most relentless cancers to thrive and resist treatment. “By focusing on ecDNA, we could cut the lifeline of these aggressive tumors, transforming a poor prognosis into a treatable condition,” he said.
Dr. Charles Swanton, deputy clinical director at the Francis Crick Institute and senior author of one of the studies, highlighted the potential of this research to reshape cancer treatments. “This work illustrates the role of circular DNA elements in enhancing cancer cells’ resilience and evading the immune system,” Swanton said. “We hope these findings will pave the way for new approaches to limit ecDNA’s role and improve patient outcomes.”
The study represents a promising step toward novel therapies that may one day help those with the most difficult-to-treat cancers, offering new pathways for hope and innovation in cancer care.
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