Cisplatin-induced pyroptosis: a double-edged sword in cancer treatment

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Wenyang Lei, Wenting Yu, Yu Zhong, Ti Li, Hongjun Xiao, S. Zong
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引用次数: 0

Abstract

Cancer is a major cause of death worldwide and a serious threat to human health. Cisplatin, a widely used first-line chemotherapeutic agent for various solid tumors, is renowned for its efficacy but is limited by significant cytotoxicity. Cisplatin triggers pyroptosis in tumor cells by activating Gasdermin proteins, thereby enhancing its anticancer efficacy. However, this same mechanism can induce pyroptosis in normal cells, causing inflammation and toxicity in healthy tissues, such as nephrotoxicity and ototoxicity. The objective of this review is to identify the major molecular targets for optimizing the cisplatin treatment window by summarizing recent advances in the pyroptosis caused by cisplatin in different cancer types and normal tissues. Among them, gasdermin D and gasdermin E are the main molecular targets involved in cisplatin-induced pyroptosis, and GSDMB also has similar effects. Future research directions include exploring targeted drug delivery systems and target regulating GSDMs (gasdermin protein family) to selectively modulate pyroptosis, thereby maximizing cisplatin’s anticancer effects while minimizing its side effects. Therefore, this review provides a comprehensive overview of cisplatin-induced pyroptosis, offering new insights into therapeutic strategies in cancer treatment.
顺铂诱导的热毒症:癌症治疗的双刃剑
癌症是全球死亡的主要原因,也是对人类健康的严重威胁。顺铂是广泛用于治疗各种实体瘤的一线化疗药物,以其疗效显著而闻名,但却受到明显的细胞毒性的限制。顺铂通过激活 Gasdermin 蛋白引发肿瘤细胞的热蛋白沉积,从而增强其抗癌功效。然而,同样的机制也会诱导正常细胞发生热变态反应,导致炎症和健康组织中毒,如肾毒性和耳毒性。本综述旨在通过总结顺铂在不同癌症类型和正常组织中引起的热蛋白沉积的最新研究进展,确定优化顺铂治疗窗口的主要分子靶点。其中,gasdermin D和gasdermin E是顺铂诱导热休克的主要分子靶点,GSDMB也有类似作用。未来的研究方向包括探索靶向给药系统和靶向调节 GSDMs(gasdermin 蛋白家族),以选择性地调节热蛋白沉积,从而最大限度地发挥顺铂的抗癌作用,同时减少其副作用。因此,本综述全面概述了顺铂诱导的热蛋白沉积,为癌症治疗策略提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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