Recent study suggests that in the acidic environment of tumor cells, the metabolic enzyme MDH1 reduces α-KG to L-2HG, increasing the level of reactive oxygen species (ROS) and inducing the oxidation and internalization of DR6 (the plasma membrane-localized death receptor), and then pro-caspase-8 and GSDMC are recruited to the internalized DR6 receptosome, which facilitates the activated-caspase-8 to cleave GSDMC, leading to pyroptosis ultimately (Zhang J.-y. This evidence concerns the gene CASP8 and neoplasm.