Hope for cancer patients, new treatment strategy targets rogue DNA

A promising drug targeting ecDNA is currently undergoing early-stage clinical trials.

American and British scientists have conducted a groundbreaking study that has sparked hopes for the treatment of some of the most aggressive forms of cancer. The research, published in Journal Nature Genetics, has identified a new approach for attacking malignant DNA fragments that drive tumor 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 resistance to treatment. By analyzing data from almost 15,000 British cancer patients across 39 different tumor types, researchers found that more than 16% of these cancer types showed ecDNA.

This discovery sheds light on how ecDNA drives cancer progression and resistance. Encouragingly, the study also identified a promising drug candidate 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 clear mechanism and plays an important role not just in breast or lung cancer, but in many types of cancer.” said Roel Verhaak, senior author of the paper, the Harvey and Kate Cushing Professor of Neurosurgery at the Yale School of Medicine and member of the Yale Cancer Center.

According to one released by Yale UniversityThe study found that ecDNA is detected more frequently after taxol-based therapies such as docetaxel and paclitaxel, which are used to treat many types of cancer. 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 studied, ecDNA was sensitive to rapid mutations. Researchers say these “hypermutations” may be one reason why cancer becomes so aggressive and difficult to treat over time. The mutations in ecDNA can help cancer cells adapt and survive better than their normal counterparts. The hope is that this research can help develop better cancer treatments.

“In the laboratory, we use drug libraries to find out what can specifically target ecDNA-containing cells,” says Verhaak. “We want to find vulnerabilities in tumors that have ecDNA, because ecDNA-targeted therapies could benefit as many as a third of all cancer patients.”

Verhaak said there are ongoing clinical trials of therapies 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.