Exosome-mediated communication and gasdermin-driven pyroptosis in colorectal cancer: Functional interactions in the tumor microenvironment.

A clear mechanistic understanding of how exosome-mediated communication interfaces with gasdermin-driven pyroptosis in colorectal cancer remains limited, particularly under heterogeneous tumor microenvironment conditions. This review integrates current experimental and clinical evidence to examine how vesicle trafficking and pyroptotic signaling converge within a shared regulatory context. Available data indicate that exosome biogenesis and cargo selection are governed by coordinated ESCRT-dependent and lipid-mediated pathways, generating heterogeneous vesicle populations that reflect intracellular signaling and metabolic states. In parallel, pyroptosis is controlled by proteolytic activation of gasdermins, where membrane pore formation spans a continuum from sublytic cytokine release to complete lytic rupture, depending on caspase activation, membrane composition, and repair capacity. Emerging evidence suggests that exosome-derived cargo modulates inflammasome priming, gasdermin expression, and intracellular signaling thresholds, thereby influencing susceptibility to pyroptotic execution. Conversely, pyroptosis-associated release of cytokines and danger signals contributes to the regulation of vesicle-mediated signaling by shaping immune activation and intercellular communication patterns. These processes are further conditioned by hypoxia, metabolic stress, and extracellular matrix organization, which collectively regulate signaling amplitude and spatial responsiveness. Overall, current findings support a context-dependent and threshold-regulated interaction between these pathways. Improved characterization of this axis may refine biomarker interpretation and inform therapeutic strategies targeting tumor-associated inflammatory signaling.