Exosomes: A Critical Tool In Cancer Therapy & Beyond

Exosomes are a subset of extracellular vesicles with an average diameter of approximately 100 nm, originate through the endosomal pathway, and carry nucleic acids, proteins, lipids, amino acids, and metabolites that can reflect the state of their parental cells; exosome research has therefore moved from a reticulocyte-maturation secretion phenomenon to a major framework for studying intercellular communication, organ homeostasis, disease progression, and biomedical applications. Exosome biogenesis involves endosome maturation, multivesicular body formation, intraluminal vesicle release, and uptake, fusion, or receptor-mediated signaling in recipient cells; Rab GTPases, ESCRT-related proteins, tetraspanins, integrins, CD9, CD63, CD81, TSG101, and ALIX are commonly used to investigate formation, cargo sorting, and characterization. Foundational studies showed that exosomes transfer mRNA and microRNA, that glioblastoma-derived microvesicles transport RNA and proteins that promote tumor growth and support biomarker discovery, and that tumor exosome integrins α6β4, α6β1, and αvβ5 regulate organotropic metastasis through organ-specific uptake, Src phosphorylation, and pro-inflammatory S100 gene expression. Therapeutic applications now focus on exosome drug delivery, nucleic acid delivery, cancer immunomodulation, liquid biopsy development, and tumor microenvironment remodeling; engineered exosomes carrying siRNA against oncogenic KRAS showed therapeutic activity in pancreatic cancer models, and brain-targeted exosome delivery of siRNA supports broader applications beyond oncology. Key unresolved barriers include EV subtype heterogeneity, proof of cellular origin, isolation and purification reproducibility, payload loading, biodistribution, potency assays, quality control, and scalable clinical manufacturing; MISEV2018 highlights the need for minimal experimental information and standardized reporting, and future work should prioritize reproducible EV characterization, mechanism-defined targeting, and clinically measurable efficacy endpoints^{[1][2][3][4][5][6][7][8][9]}.