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<p>Disulfidptosis, a recently identified form of disulfide-dependent cell death, has emerged as a key regulator of cancer progression and therapy resistance. This review examines the molecular mechanisms connecting the redox balance within the tumor microenvironment (TME), outlines its crosstalk with traditional cell death pathways, and highlights its promise as a therapeutic strategy. Current evidence indicates that disulfidptosis is driven by glutathione (GSH) depletion and thiol-disulfide exchange imbalance, leading to endoplasmic reticulum stress and tumor cell vulnerability. Translational applications—including small-molecule activators and combination therapies—are discussed, alongside challenges in clinical translation and future research directions.</p>

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Disulfidptosis in cancer: from redox stress to therapeutic strategy

  • 期刊论文

  • 发表日期：

    2025年10月28日

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  • Xinpei Deng,
  • Chengyi Zhang,
  • Jindong Xie,
  • Binbin Tang,
  • Xingliang Tan,
  • Yutian Zou

摘要

Disulfidptosis, a recently identified form of disulfide-dependent cell death, has emerged as a key regulator of cancer progression and therapy resistance. This review examines the molecular mechanisms connecting the redox balance within the tumor microenvironment (TME), outlines its crosstalk with traditional cell death pathways, and highlights its promise as a therapeutic strategy. Current evidence indicates that disulfidptosis is driven by glutathione (GSH) depletion and thiol-disulfide exchange imbalance, leading to endoplasmic reticulum stress and tumor cell vulnerability. Translational applications—including small-molecule activators and combination therapies—are discussed, alongside challenges in clinical translation and future research directions.