Molecular mechanisms of exosome-mediated drug resistance in central nervous system tumours

Exosomes are 30-150 nm extracellular vesicles released via fusion of multivesicular bodies with the plasma membrane and enriched in selectively sorted proteins, lipids and nucleic acids that reflect both donor-cell state and regulated packaging pathways. In central nervous system (CNS) tumours, exosome-mediated communication is increasingly recognised as a scalable mechanism by which malignant cells coordinate adaptation to therapy across cellular and anatomical barriers, including the blood-brain barrier. This review synthesises current evidence linking exosome biogenesis and cargo selection (ESCRT-associated factors, tetraspanins, Rab GTPases, RNA-binding proteins) with key resistance phenotypes in glioblastoma and other CNS tumour entities. We outline four convergent routes by which exosomes blunt therapeutic efficacy: horizontal transfer of resistance determinants, rapid activation of pro-survival signalling hubs, tumour-microenvironment remodeling, vesicle-enabled "drug scavenging", where cytotoxic agents and/or efflux machinery are sequestered and exported, lowering effective intracellular drug exposure. Finally, we discuss translational opportunities and constraints, highlighting exosome-based liquid biopsy strategies in CSF and blood and therapeutic concepts targeting vesicle biogenesis, release or uptake, while emphasizing the need for rigorous EV characterization and reporting standards to accelerate clinical implementation.