Targeting extrachromosomal DNA in human cancers
Summary
Extrachromosomal DNAs (ecDNAs) are acentric circular DNA elements that frequently mediate oncogene amplification and genomic rearrangements in human cancers. Found across diverse adult and paediatric malignancies, ecDNA drives rapid tumour evolution, metabolic adaptation and treatment resistance. Its presence in precancerous lesions and association with poor outcome underscore the need for improved detection and therapeutic targeting. Recent advances have substantially expanded our underst
Content
# Targeting extrachromosomal DNA in human cancers
*Published: 2026 May*
Extrachromosomal DNAs (ecDNAs) are acentric circular DNA elements that
frequently mediate oncogene amplification and genomic rearrangements in human
cancers. Found across diverse adult and paediatric malignancies, ecDNA drives
rapid tumour evolution, metabolic adaptation and treatment resistance. Its
presence in precancerous lesions and association with poor outcome underscore
the need for improved detection and therapeutic targeting. Recent advances have
substantially expanded our understanding of ecDNA biology, revealing mechanisms
underlying oncogene plasticity and treatment failure. This Review synthesizes
key findings on ecDNA biology, the challenges faced by current therapeutic and
detection approaches and the recent discoveries that point to emerging
therapeutic vulnerabilities. We propose future directions to ecDNA-focused
therapeutic development, including the utility of chemical proteomics
approaches, and discuss efforts required to integrate ecDNA diagnostics into the
clinic, presenting a roadmap from bench to bedside.
DOI: 10.1038/s41573-025-01369-0