Wed Dec 04 00:00:00 UTC 2024: ## New Research Reveals Extrachromosomal DNA’s Crucial Role in Cancer and Potential for New Treatments

**Chennai, India – December 4, 2024** – A groundbreaking study published in *Nature* reveals the significant role of extrachromosomal DNA (ecDNA) in cancer development and progression. For decades dismissed as insignificant, ecDNA, circular fragments of DNA found outside chromosomes, is now understood to be present in a significant percentage of cancers, influencing tumor growth, drug resistance, and metastasis.

Three papers published by the international collaboration eDyNAmiC, led by Stanford University’s Paul Mischel, detail ecDNA’s mechanisms. The research shows ecDNA’s formation is triggered by various factors, including smoking and exposure to certain substances. Analysis of nearly 15,000 cancer patient samples from the UK’s 100,000 Genomes Project revealed ecDNA’s presence in approximately 17% of tumors, with higher prevalence in liposarcomas, brain, and breast cancers. Furthermore, ecDNA prevalence increased after chemotherapy and correlated with poorer patient outcomes.

The studies overturn established genetic principles. ecDNA, containing multiple copies of oncogenes, moves freely within the cell nucleus, forming hubs of gene expression, and violates Mendel’s third law of independent assortment by clustering during cell division – a phenomenon termed the “jackpot effect.” This allows for enhanced gene interactions and advantageous genetic combinations across cell generations.

Critically, the research identified a potential vulnerability. The heightened gene activity from ecDNA creates cellular conflict, prompting the overproduction of the CHK1 protein for DNA repair. Targeting CHK1 with drugs like BBI-2779 selectively kills ecDNA-driven cancer cells, demonstrating promising therapeutic potential. Boundless Bio, a biotechnology company co-founded by Mischel and Chang, is actively pursuing clinical translation of these findings, offering hope for new treatments for cancers like glioblastoma, ovarian, and lung cancers where current therapies are often ineffective.

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