“Our research suggests that ecDNA helps tumors become more aggressive,” said senior author of the paper, Roel Verhaak, the Harvey and Kate Cushing Professor of Neurosurgery at Yale School of Medicine and member of Yale Cancer Center. “EcDNA has a distinct mechanism and plays an important role, not just for breast or lung cancer, but across many cancer types.”

The study found that ecDNA is detected more often after taxol-based therapies such as docetaxel and paclitaxel, which is used for treatment of many cancer types. The researchers also noticed that when they looked at the same cancer over time, ecDNA was more likely to stick around than DNA changes on the regular chromosomes.

In the advanced cancers that were studied, ecDNA was prone to rapid mutations. Researchers say these "hypermutations" could be one of the reasons why cancer becomes so aggressive and difficult to treat as time goes on. The mutations in ecDNA may help cancer cells adapt and survive better than their normal counterparts. The hope is that this research can aid in the development of better cancer treatments.

“In the lab, we’re using drug libraries to find out what can specifically target ecDNA-containing cells,” said Verhaak. “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.”

Verhaak said there are ongoing clinical trials involving therapies that are designed to specifically target ecDNA in tumors.

Yale Cancer Center’s So Yeon Kim and Kevin Johnson joined Verhaak as co-authors on the study. Hoon Kim, a former postdoctoral trainee in the Verhaak lab and now a professor at Sungkyunkwan University in Seoul, South Korea, co-led the project.