Extrachromosomal DNA and cancer: function, formation, and clinical implications

TL;DR

This paper reviews extrachromosomal DNA in cancer, its role in tumor development, and potential therapies targeting it.

Contribution

The paper provides a comprehensive review of ecDNA's role in cancer and highlights emerging therapeutic strategies.

Findings

Cancer-associated ecDNAs are large, clonal, and carry complete oncogenes.

ecDNA contributes to tumor heterogeneity and therapeutic resistance through gene amplification and regulation.

Five emerging therapeutic approaches targeting ecDNA are summarized.

Abstract

Extrachromosomal DNA (ecDNA) is a circular, double-stranded DNA molecule distinct from chromosomal DNA, primarily found in cancer cells as a subtype of extrachromosomal circular DNA (eccDNA). Unlike eccDNAs found in normal cells, cancer-associated ecDNAs are large, clonal, and carry complete oncogenes. These ecDNAs are increasingly recognized as crucial drivers of cancer pathogenesis, contributing significantly to the evolution of tumor heterogeneity and the acquisition of therapeutic resistance through mechanisms such as high-level gene amplification and altered gene regulation. Historically, the understanding of these mobile genetic elements in cancer has been limited. This review synthesizes current knowledge on ecDNA’s structural and functional features, formation mechanisms and roles in cancer initiation, progression and therapeutic resistance. Moreover, we summarize five emerging therapeutic approaches that target ecDNA to inform future cancer research and precision medicine.

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