The emerging clinical potential of circulating extracellular vesicles for non-invasive glioma diagnosis and disease monitoring.

Diffuse gliomas (grades II-IV) are amongst the most frequent and devastating primary brain tumours of adults. Currently, patients are monitored by clinical examination and radiographic imaging, which can be challenging to interpret and insensitive to early signs of treatment failure and tumour relapse. While brain biopsy and histologic analysis can evaluate disease progression, serial biopsies are invasive and impractical given the cumulative surgical risk, and may not capture the complete molecular landscape of an evolving tumour. The availability of a minimally invasive 'liquid biopsy' that could assess tumour activity and molecular phenotype in situ has the potential to greatly enhance patient care. Circulating extracellular vesicles (EVs) hold significant promise as robust disease-specific biomarkers accessible in the blood of patients with glioblastoma and other diffuse gliomas. EVs are membrane-bound nanoparticles shed from most if not all cells of the body, and carry DNA, RNA, protein, and lipids that reflect the identity and molecular state of their cell-of-origin. EVs can cross the blood-brain barrier and their release is upregulated in neoplasia. In this review, we describe the current knowledge of EV biology, the role of EVs in glioma biology and the current experience and challenges in profiling glioma-EVs from the circulation.