Exosomes in Cancer: The Biology, Function, Diagnosis, and Therapy

Exosomes are central mediators of intercellular communication in the tumor microenvironment, transferring proteins, lipids, metabolites, and nucleic acids that regulate cancer progression. Recent advances in multi-omics and extracellular vesicle profiling have revealed substantial molecular and functional heterogeneity, extending beyond classical membrane-bound exosomes to nonmembranous extracellular nanoparticles such as exomeres and supermeres. Here, we provide a pan-cancer synthesis of exosome biology, integrating mechanisms of biogenesis, cargo sorting, and secretion with emerging concepts of extracellular nanoparticle diversity. We examine how tumor-derived exosomes remodel local and distant microenvironments by promoting angiogenesis, metabolic reprogramming, immune suppression, premetastatic niche formation, and cancer-associated cachexia. We also discuss the relative contributions of active organotropic targeting and passive spatiotemporal accumulation to metastatic dissemination, together with tissue-specific mechanisms governing endothelial barrier crossing, myeloid-cell reprogramming, and intercellular network integration. Clinically, we evaluate exosome-based liquid biopsy, molecular subtyping, engineered delivery systems, and strategies that inhibit endogenous vesicle production or circulation. Finally, we outline key translational challenges, including single-vesicle heterogeneity, limited intravital tracking, and the absence of standardized cGMP manufacturing and analytical frameworks across diverse tumor types and clinically relevant biological contexts worldwide. This review defines a roadmap for exosome-guided precision oncology.