Extracellular Vesicle-Associated miRNAs in Glioblastoma: Mechanisms, Biomarkers, Therapies, and Links to Neurodegeneration

Extracellular vesicles (EVs) facilitate intercellular communication in glioblastoma (GBM) by transferring microRNAs (miRNAs). GBM is the most aggressive primary brain tumor in adults, and despite multimodal therapy, the median survival remains approximately 15 months. Current diagnostic approaches, including contrast-enhanced MRI, are insufficient to reliably distinguish true tumor progression from pseudoprogression. Moreover, therapeutic efficacy is limited by intratumoral heterogeneity, acquired resistance, and the restrictive nature of the blood-brain barrier (BBB). In this context, EV-associated miRNAs (EV-miRNAs) contribute to GBM progression by regulating proliferation, angiogenesis, invasion, therapeutic resistance, and immune evasion. Notably, several EV-miRNAs are dysregulated in both GBM and neurodegenerative diseases (NDDs), suggesting shared molecular pathways across central nervous system (CNS) disorders. Circulating tumor-derived EV-miRNAs represent promising liquid biopsy biomarkers for diagnosis, prognosis, and longitudinal treatment monitoring. Beyond their biomarker potential, EVs can be engineered as nanocarriers capable of crossing the BBB to deliver therapeutic cargo, including inhibitors of oncogenic miRNAs (e.g., miR-21) or tumor-suppressive miRNAs (e.g., miR-124). This review summarizes the molecular functions, biomarker applications, and therapeutic strategies of EV-miRNAs in GBM. We further discuss current challenges related to methodological standardization, scalable production, and clinical translation. Collectively, advancing the understanding and clinical implementation of EV-miRNAs may provide new opportunities for precision diagnostics and therapeutic innovation in GBM.