A novel therapeutic avenue: pharmacological induction of tumor cell pyroptosis.

Emerging preclinical evidence indicates that pharmacological induction of tumor pyroptosis promotes immune responses, representing a new therapeutic avenue for relapsed/refractory cancer patients. For example, a recent study in Communications Medicine has demonstrated that histone deacetylase inhibitors de-repress transcription of a tumor suppressor GSDME in B-cell lymphoma cells, and synergize with cisplatin and etoposide to promote GSDME cleavage by caspase-3 and subsequent pyroptosis of lymphoma cells. Furthermore, the anti-lymphoma efficacy of this combination therapy in vivo depends on CD8 T cells. This article provides a brief introduction of the pyroptosis pathway in cancer, comments on this promising 'One action, two benefits' therapeutic strategy for cancer treatment, and discusses the significance and unaddressed questions in recent therapeutic studies targeting pyroptosis-suppressing mechanisms in cancer.