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

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.