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<p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月19日

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  • Yucai Wu,
  • Rui Rui,
  • Tai Tian,
  • Jiaying Zheng,
  • Shiming He,
  • Liqun Zhou,
  • Xuesong Li,
  • Yanqing Gong

摘要

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.

Graphical Abstract