Breaking through the glioblastoma micro-environment via extracellular vesicles

Glioblastoma (GBM) is the most common and most aggressive brain tumour. Prognosis remains poor, despite the combined treatment of radio- and chemotherapy following surgical removal. GBM cells coexist with normal non-neoplastic cells, including endothelial cells, astrocytes and immune cells, constituting a complex and dynamic tumour micro-environment (TME). Extracellular vesicles (EVs) provide a critical means of bidirectional inter-cellular communication in the TME. Through delivery of a diverse range of genomic, lipidomic and proteomic cargo to neighbouring and distant cells, EVs can alter the phenotype and function of the recipient cell. As such, EVs have demonstrated their role in promoting angiogenesis, immune suppression, invasion, migration, drug resistance and GBM recurrence. Moreover, EVs can reflect the phenotype of the cells within the TME. Thus, in conjunction with their accessibility in biofluids, they can potentially serve as a biomarker reservoir for patient prognosis, diagnosis and predictive therapeutic response as well as treatment follow-up. Furthermore, together with the ability of EVs to cross the blood-brain barrier undeterred and through the exploitation of their cargo, EVs may provide an effective mean of drug delivery to the target site. Unveiling the mechanisms by which EVs within the GBM TME are secreted and target recipient cells may offer an indispensable understanding of GBM that holds the potential to provide a better prognosis and overall quality of life for GBM patients.