Manipulation of cancer cell pyroptosis for therapeutic approaches: challenges and opportunities

Abstract Remarkable advances have been achieved following discoveries that gasdermins are the executioners of pyroptosis. The pyroptotic process consists a subcellular permeabilization phase and a cell lysis phase, the latter of which is irreversible. Besides immune cells, pyroptosis has also been observed in cancer cells, which exhibit distinct mechanisms compared to canonical immune cell pyroptosis. Although chronic cancer cell pyroptosis fuels tumor growth, intense pyroptotic cell death in tumor cells enhances anticancer immunity by promoting killer lymphocytes infiltration. Triggering pyroptosis in cancer cells is emerging as a promising strategy for cancer treatment. In this review, we introduce the process of cancer cell pyroptosis and its role in antitumor immunity, discuss the translation of these insights into therapies, and highlight current challenges and opportunities in the investigation of cancer cell pyroptosis.