PANoptosis in hepatocellular carcinoma: Underlying mechanisms

PANoptosis is an inflammatory programmed cell death pathway possessing critical characteristics of apoptosis, pyroptosis, and necroptosis. It is regulated by PANoptosome complexes, involves interaction between these three key programmed cell death pathways, yet is distinct from any alone. PANoptosis holds vital significance in liver-related diseases, particularly hepatocellular carcinoma (HCC). This article summarizes research on the mechanism and treatments of PANoptosis in HCC. Current research has partially elucidated PANoptosis-related mechanisms in HCC and identified several molecules modulating it. Therapeutic strategies targeting PANoptosis hold significant promise. Investigations into these critical molecules have led to the development of traditional targeted drug therapies and emerging strategies like nanotechnology-based immunocombination therapies. However, there are still challenges in the mechanistic and pharmacological studies of PANoptosis in HCC, including the bidirectional regulation of key apoptotic factors, specific molecular mechanisms, and preclinical models. This article offers a new orientation for studying the pathogenesis and potential therapeutic strategies for HCC.