Targeting ATM kinase: a promising strategy to disrupt ecDNA maintenance in cancer

Zhuoyang Zhao; Shunichi Takeda

doi:10.1007/s42764-025-00165-9

Genome Instability & Disease ›› :1 -5. DOI: 10.1007/s42764-025-00165-9

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Targeting ATM kinase: a promising strategy to disrupt ecDNA maintenance in cancer

Zhuoyang Zhao ¹
, Shunichi Takeda ¹^,²^,^a

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Abstract

In their recent Cell publication, Kang et al. shed light on a critical yet poorly understood aspect of cancer biology: how tumor cells preserve oncogenic extrachromosomal DNA (ecDNA). The study reveals that DNA topoisomerases frequently introduce double strand breaks into ecDNA, triggering its rapid degradation. Importantly, the authors identify a DNA damage repair pathway that counteracts this degradation by re-circularizing ecDNA. Given the potent oncogenic potential of ecDNA, these findings not only deepen our mechanistic understanding of ecDNA maintenance but also highlight promising new therapeutic targets in ecDNA-positive cancers.

Keywords

Extrachromosomal DNA / Cancer / DNA damage response / ATM kinase / Topoisomerase

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Zhuoyang Zhao, Shunichi Takeda. Targeting ATM kinase: a promising strategy to disrupt ecDNA maintenance in cancer. Genome Instability & Disease 1-5 DOI:10.1007/s42764-025-00165-9

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