CASP8 and cancer: In an acidic environment, α-ketoglutarate (α-KG) is inhibited by MDH1 and transformed into L-2HG, which increases the level of ROS, leads to the oxidation of the death receptor DR6 located in plasma membrane, triggers its endocytosis, recruits caspase-8-mediated GSDMC cleavage, and finally induces pyroptosis.81 Treatment with α-KG derivative DMΑ-KG can further improve the level of ROS and make cancer cells that originally resisted pyroptosis more vulnerable to pyroptosis induced by α-KG.81 It reveals that GSDMC has potential clinical value in tumor treatment.