Organelles and cancer cell pyroptosis: overview and perspectives

Abstract Pyroptosis, a gasdermin (GSDM)-mediated immunogenic programmed cell death modality, manifests through characteristic membrane permeabilization and proinflammatory cytokine release. Pyroptosis exhibits dual therapeutic advantages by remodeling the tumor microenvironment and potentiating systemic anti-tumor immunity, positioning it as a pivotal focus in cancer immunotherapy. However, researchers still focus current pyroptosis induction strategies predominantly on single molecular targets and have not sufficiently analyzed the inter-organelle communication networks that govern pyroptotic signaling cascades. This review provides a systematic exploration of organelle-specific ultrastructural alterations during pyroptosis progression and the molecular machinery regulating organelle-mediated pyroptotic pathways. We synthesize recent advances in organelle-targeted pyroptosis induction strategies, elucidating how inter-organelle crosstalk networks to enhance therapeutic efficacy. We aim to provide translational approaches for optimizing cancer treatment paradigms.