Stanford researchers and their global collaborators have uncovered a groundbreaking discovery in cancer biology, revealing the significant role of extrachromosomal DNA (ecDNA) in driving human cancers. Published in three papers in Nature on November 6, these studies highlight the prevalence and impact of ecDNA in nearly 15,000 cancer samples, challenge traditional genetic inheritance laws, and introduce a novel cancer therapy currently undergoing clinical trials.
Led by Paul Mischel, MD, and Howard Chang, MD, PhD, the eDyNAmiC research team has shown that ecDNA, small DNA circles often containing oncogenes, play a central role in tumor growth and drug resistance. Initially dismissed as inconsequential, ecDNA is now recognized as a key factor in cancer metastasis and poor prognosis. The research demonstrates that nearly 17% of tumors contain ecDNA, and its presence is linked to worse outcomes after treatment.
In one study, ecDNA circles were shown to collaborate with other ecDNAs to enhance cancer cell growth, a concept that challenges the conventional view that ecDNA alone drives cancer. The second paper revealed a new mode of inheritance, overturning Gregor Mendel’s law of independent assortment. Instead of segregating randomly during cell division, ecDNAs remain linked, enabling cancer cells to inherit advantageous combinations of ecDNA, fueling tumor progression and drug resistance.
The third study explores a promising new cancer treatment. Researchers discovered that inhibiting a protein called CHK1, which regulates cell division, selectively kills ecDNA-containing tumor cells. This approach is currently in clinical trials, offering hope for patients with cancers driven by ecDNA.
This series of studies marks a pivotal moment in cancer research, providing critical insights into cancer initiation and progression while offering new therapeutic avenues to target the mechanisms that drive cancer. The findings represent the potential for transforming the treatment and understanding of cancer in the future.
NEWS DESK
PRESS UPDATE