鉴于癌细胞的持续增殖潜力，诱导细胞死亡是肿瘤治疗的一种潜在策略。萎缩性坏死是一种以内质网（ER）和/或线粒体肿胀和胞质空泡化为特征的细胞死亡方式，尚未得到深入研究。相当多的证据表明，各种化学化合物可以触发萎缩性坏死，尤其是在癌细胞中，从而凸显了这种非经典细胞死亡方式在肿瘤治疗中的潜在应用。尽管有这些发现，但我们对萎缩性坏死在癌症中的作用仍存在重大的认识差距。在本综述中，我们总结了化学化合物诱导的萎缩性坏死的当前知识。内质网和线粒体是化学化合物诱导的萎缩性坏死中两个主要的反应器官，其可以通过降低蛋白降解、破坏巯基平衡、线粒体钙离子超载以及增加活性氧物质的产生来触发。我们还讨论了该领域发展的障碍和进一步研究的方向。合理利用萎缩性坏死可能帮助我们开发肿瘤治疗的新范式。©2023年作者，上海药物研究所中国科学院和中国药理学会独家许可。

Due to the sustained proliferative potential of cancer cells, inducing cell death is a potential strategy for cancer therapy. Paraptosis is a mode of cell death characterized by endoplasmic reticulum (ER) and/or mitochondrial swelling and cytoplasmic vacuolization, which is less investigated. Considerable evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, thus highlighting the potential application of this non-classical mode of cell death in cancer therapy. Despite these findings, there remain significant gaps in our understanding of the role of paraptosis in cancer. In this review, we summarize the current knowledge on chemical compound-induced paraptosis. The ER and mitochondria are the two major responding organelles in chemical compound-induced paraptosis, which can be triggered by the reduction of protein degradation, disruption of sulfhydryl homeostasis, overload of mitochondrial Ca2+, and increased generation of reactive oxygen species. We also discuss the stumbling blocks to the development of this field and the direction for further research. The rational use of paraptosis might help us develop a new paradigm for cancer therapy.© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.