Triggering Pyroptosis in Cancer

Abstract

Pyroptosis is an inflammatory programmed cell death recently identified as a crucial cellular process in various diseases, including cancers. Unlike other forms of cell death, canonical pyroptosis involves the specific cleavage of gasdermin by caspase-1, resulting in cell membrane damage and the release of the pro-inflammatory cytokines IL-1β and IL-18. Initially observed in innate immune cells responding to external pathogens or internal death signals, pyroptotic cell death has now been observed in numerous cell types. Recent studies have extensively explored different ways to trigger pyroptotic cell death in solid tumors, presenting a promising avenue for cancer treatment. This review outlines the mechanisms of both canonical and noncanonical pyroptosis pertinent to cancer and primarily focuses on various biomolecules that can induce pyroptosis in malignancies. This strategy aims not only to eliminate cancer cells but also to promote an improved tumor immune microenvironment. Furthermore, emerging research indicates that targeting pyroptotic pathways may improve the effectiveness of existing cancer treatments, making them more potent against resistant tumor types, offering new hope for overcoming treatment resistance in aggressive malignancies.

Keywords

• cancer
• pyroptosis
• cell death
• chemotherapy drugs
• caspase-1
• gasdermin