Work

Pyroptosis in cancer: a dual regulator of tumor cell fate and immune activation

Year: 2026

Type: article

Abstract: Pyroptosis is a form of programmed cell death (PCD) that triggers inflammation. Pyroptosis is activated by specific inflammasomes and caspases, leading to the cleavage of gasdermin protein families, especially gasdermin D (GSDMD) and gasdermin E (GSDME). While pyroptosis has been extensively linked to innate immunity and diseases, such as atherosclerosis, the role in cancer remains an area of active investigation. Studies have suggested that pyroptosis influences tumor behavior, including proliferation and invasion, across different tissue types and genetic backgrounds. This process occurs through both canonical and non-canonical pathways involving GSDMD and GSDME. Tumors tend to thrive in the chronic inflammatory environment created by pyroptosis but tumors are more likely to be eradicated if pyroptosis occurs suddenly and extensively. Indeed, targeting pyroptosis pathways holds promise as an anticancer strategy. To date, several drugs are found to have the ability of inducing pyroptosis to enhance tumor clearance. Moreover, pyroptosis-related genes (PRGs) have emerged as valuable biomarkers for prognosis and monitoring the tumor microenvironment (TME). This review explores the mechanisms underlying endogenous and exogenous pyroptosis in cancer, examines the dual role within tumors, discusses the potential for targeting pyroptosis in cancer treatment and prognosis, and highlights the interactions between pyroptosis and other forms of PCD in cancer.

Source: Cancer Biology and Medicine

DOI: 10.20892/j.issn.2095-3941.2025.0826