Fig. 6

Mechanism of chemotherapy drugs and nonchemotherapy drugs in pyroptosis pathway in tumor cells. a Chemotherapy drugs mainly induce GSDME-mediated pyroptosis via activation of pro-caspase-3, while caspase-3 can further promote apoptosis. Formation of GSDME pore leads to cytolysis, cytokine release, and activation of immune cells like dendritic cells, CD8⁺ T cells, and NK cells. GzmA secreted from CD8⁺ T cells and NK cells induce GSDMB-mediated pyroptosis while CAR-T cells can activate caspase-3 in target cells and release GzmB, promoting GSDME-mediated pyroptosis. Chemo-antibiotic drugs help increase the expression of GSDMC and nuclear PD-L1, and with the help of p-Stat3, they together upregulate the expression of GSDMC. Later, caspase-8 specifically cleaves GSDMC and eventually induces pyroptosis. b Mechanisms of nonchemotherapy drugs are more complex. Drugs like dioscin, galangin, BRAFi/MEKi, etc. induce GSDME-mediated pyroptosis and release proinflammatory cytokines from pyroptotic or apoptotic pores, which could subsequently initiate the activation of immune systems. Meanwhile, other reagents like anthocyanin and sesamin mainly exert their role in pyroptosis via GSDMD pathway in tumor cells