GSDME and cancer: To be specific, chloroquine (CQ) and hydroxychloroquine (HCQ) inhibit autophagosome degradation by inhibiting the lysosomal acidification.362 These drugs, especially HCQ, have been re-used in many clinical trials for the treatment of various cancers.363–365 Metformin inhibits cancer cell proliferation by inducing indirect pyroptosis activation through CASP3.366 In detail, metformin causes mitochondrial dysfunction and activates the AMPK/sirtuin1/NF-κB pathway, promoting the accumulation of Bax which results in CASP3 activation and GSDME cleavage.