Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer

Abstract

As a type of regulated cell death (RCD) mode, pyroptosis plays an important role in several kinds of cancers. Pyroptosis is induced by different stimuli, whose pathways are divided into the canonical pathway and the noncanonical pathway depending on the formation of the inflammasomes. The canonical pathway is triggered by the assembly of inflammasomes, and the activation of caspase-1 and then the cleavage of effector protein gasdermin D (GSDMD) are promoted. While in the noncanonical pathway, the caspase-4/5/11 (caspase 4/5 in humans and caspase 11 in mice) directly cleave GSDMD without the assembly of inflammasomes. Pyroptosis is involved in various cancers, such as lung cancer, gastric cancer, hepatic carcinoma, breast cancer, and colorectal carcinoma. Pyroptosis in gastric cancer, hepatic carcinoma, breast cancer, and colorectal carcinoma is related to the canonical pathway, while both the canonical and noncanonical pathway participate in lung cancer. Moreover, simvastatin, metformin, and curcumin have effect on these cancers and simultaneously promote the pyroptosis of cancer cells. Accordingly, pyroptosis may be an important therapeutic target for cancer.