Yale researchers have identified extrachromosomal DNA (ecDNA) as a potential target for future cancer therapies, with findings suggesting its significant role in tumor aggression and resistance.
Yale Cancer Center researchers have identified extrachromosomal DNA (ecDNA) as a distinguishing factor in more aggressive and advanced cancers, a breakthrough that could revolutionize future cancer therapies.
The team analyzed over 8,000 tumor samples, leveraging data from The Cancer Genome Atlas, the International Cancer Genomics Consortium, the Hartwig Medical Foundation and the Glioma Longitudinal Analysis Consortium. They discovered a higher concentration of ecDNA in previously treated tumors, suggesting that ecDNA may bestow a survival advantage on these cancer cells.
“Our research suggests that ecDNA helps tumors become more aggressive,” senior author Roel Verhaak, the Harvey and Kate Cushing Professor of Neurosurgery at Yale School of Medicine and member of Yale Cancer Center, said in a news release. “EcDNA has a distinct mechanism and plays an important role, not just for breast or lung cancer, but across many cancer types.”
The study, published in the October 14 issue of Nature Genetics, indicated that ecDNA is more frequently found following taxol-based therapies, such as docetaxel and paclitaxel, widely used in cancer treatment. A particularly alarming discovery was the propensity for ecDNA to undergo rapid mutations, termed “hypermutations,” potentially making cancer cells more adaptable and harder to eradicate.
The researchers believe that targeting ecDNA could be a game-changer in developing more effective cancer treatments. In ongoing clinical trials, therapies specifically designed to target ecDNA in tumors are in the spotlight, aiming to exploit vulnerabilities in these aggressive cancer cells.
“In the lab, we’re using drug libraries to find out what can specifically target ecDNA-containing cells,” Verhaak added. “We want to find vulnerabilities in tumors that have ecDNA, as ecDNA-targeting therapies could benefit as many as a third of all cancer patients.”
As the battle against cancer continues, these findings provide a glimmer of hope that new, more effective treatments are on the horizon, potentially improving the prognosis for countless patients globally.