Extrachromosomal DNA (ecDNA), which exists outside of chromosomes, has been identified as a significant factor in cancer progression, particularly in advanced and treatment-resistant tumors.

Once thought to be a minor feature present in only 1.4% of tumors, ecDNA is now detected in over 17% of tumor genomes across 39 different types.

Notably, ecDNA molecules produce mRNA at a rate four times greater than genes located on chromosomes, which contributes to the growth and adaptability of cancer cells.

This phenomenon is further complicated by the clustering of ecDNAs, which allows oncogenes located on different ecDNAs to synergistically enhance each other's expression.

During cell division, the inheritance of ecDNA is chaotic, often resulting in daughter cells inheriting more copies of oncogenes than their parents, thereby promoting tumor evolution.

Recent research led by physician-scientists Howard Y. Chang and Paul Mischel demonstrates that ecDNA provides tumors with a genetic advantage by enabling oncogene expression that bypasses traditional inheritance rules.

One promising strategy involves using a CHK1 inhibitor in combination with other drugs, which has shown potential in selectively destroying ecDNA-positive cancer cells.

This groundbreaking research, funded by Cancer Grand Challenges, includes three papers published on November 6, 2024, detailing the mechanisms by which ecDNA contributes to cancer growth and resilience.

Future studies will also explore non-cancerous ecDNA in fungi, which may uncover new vulnerabilities to target in cancer therapy.

Targeting the transcription of ecDNA could disrupt its inheritance pattern, leading to a more random distribution among daughter cells and presenting a potential therapeutic target.