As it faces off against the body, cancer cheats. New research investigates one of its more audacious tricks: stashing cancer-driving genes in circular

How ecDNA Fuels Cancer by Breaking the Laws of Biology | HHMI

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2024-11-15 20:00:03

As it faces off against the body, cancer cheats. New research investigates one of its more audacious tricks: stashing cancer-driving genes in circular pieces of DNA outside chromosomes.  

A trio of new studies with funding from Cancer Grand Challengesexternal link, opens in a new tab reveals the unfair advantage this extrachromosomal DNA, or ecDNA, grants tumors. Physician-scientist Howard Y. Chang, a Howard Hughes Medical Institute Investigator, co-led two of the studies along with Paul Mischelexternal link, opens in a new tab , a fellow Stanford University colleague who served as a lead on all three papersexternal link, opens in a new tab published on November 6, 2024.

“There are rules normal cells follow. One of the ways cancer wins is that it doesn’t play by the same rules,” Chang says. “What we are doing is figuring out what extra moves it has in its repertoire.”

Normal human cells generally keep their DNA in chromosomes. But that’s hardly the only way ecDNA disregards norms. Research by Chang and Mischel’s team delineates how it violates one of the fundamental principles that govern inheritance to aid tumors’ growth and make them more resilient.  Together with international collaborators, they show the scope of ecDNA’s contribution to cancer, especially to the most pernicious cases. The group also reports a strategy for developing therapies that target ecDNA in order to outmaneuver the tumors that contain it. 

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