A promising drug targeting ecDNA is currently undergoing early-stage clinical trials.
US and UK scientists have conducted a groundbreaking study that has ignited hope for treating some of the most aggressive forms of cancer. The research, published in Journal Nature Genetics, has identified a novel approach to targeting rogue DNA fragments that fuel tumour growth and resistance to chemotherapy.
Scientists discovered that many difficult-to-treat cancers contain extrachromosomal DNA (ecDNA), small loops of genetic material that are essential for tumor survival and treatment resistance. By analyzing data from nearly 15,000 UK cancer patients across 39 different tumor types, researchers found that over 16% of these cancers exhibited ecDNA.
This discovery sheds light on how ecDNA drives cancer progression and resistance. Encouragingly, the study also identified a promising drug candidate that is currently undergoing early-stage clinical trials. This drug has the potential to selectively eliminate cancer cells containing ecDNA, preventing the rapid development of drug resistance.
“Our research suggests that ecDNA helps tumors become more aggressive. EcDNA has a distinct mechanism and plays an important role, not just for breast or lung cancer, but across many cancer types,” said Roel Verhaak, senior author of the paper, the Harvey and Kate Cushing Professor of Neurosurgery at Yale School of Medicine and member of Yale Cancer Center.
As per a release by Yale University, 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.
This breakthrough offers a new avenue for cancer treatment and could significantly improve outcomes for patients with aggressive forms of the disease.
