The Role of Pyroptosis in Colorectal Cancer: From Mechanisms to Therapeutic Opportunities

Colorectal cancer is a malignant tumor with high incidence and mortality, which caused more than 1.9 million new cases of colorectal cancer (including anal cancer) and 904,000 deaths in 2022, making colorectal cancer the third-highest incidence and second-highest mortality in cancer worldwide. Conventional treatments including chemotherapy, radiotherapy and surgery have achieved certain results, but there is room for improvement. Pyroptosis is a newly discovered programmed death that induces cell death by cleaving gasdermins through caspase, making the cell form non-selective pores, undergoing cytoplasm flattening caused by plasma membrane leakage and finally leading to death. It can be induced by the following pathways including canonical pathway, non-canonical pathway, apoptotic caspases-mediated pathway and granzymes-mediated pathway. Pyroptosis is often associated with the detection, prognosis, and treatment of colorectal cancer. In canonical pathway, the common inflammasomes including NLRP3, NLRP1, NLRC4, AIM2 and Pyrin are related to the detection and prognosis of colorectal cancer. In terms of the treatment of colorectal cancer, most studies focus on the GSDMD-mediated and GSDME-mediated pyroptosis therapy, while there are relatively few studies on the treatment of colorectal cancer mediated by other gasdermin families, such as GSDMB. The pyroptosis therapy in colorectal cancer involves the drug, natural-occurring substances, chemotherapy, nanotechnology, radiotherapy, virus, and other novel treatments such as photodynamic therapy (PDT). This article explores the mechanisms of pyroptosis and its research on colorectal cancer detection and prognosis, focusing on the research related to pyroptosis and colorectal treatment, and provides an outlook on the future of pyroptosis and colorectal cancer treatment.