Extracellular vesicle proteomics in brain solid tumors: future strategy for personalized medicine.

Brain solid tumors are a leading cause of cancer-related mortality at all ages. The updated 2021WHO Central Nervous System tumor classification is based on genomic diagnostics. Nonetheless, extracellular vesicles (EVs) proteomics is a platform for protein biomarker discovery in brain tumor patient management. Tumor metabolic reprogramming, also through epigenetic mechanisms, is central to cancer. EVs transfer proteins and nucleic acids that relay the metabolic and redox state of the parent cells. This review addresses the biomarker discovery and translation focusing on recent (from 2022-2024 PubMed) proteomic studies of EVs in brain tumor patients, selected for their focus on metabolic aspects. The most treatable adult brain tumor is isocitrate dehydrogenase-mutated glioma. Minimally invasive collection of EVs from cerebrospinal fluid or prospectively blood allows proteomic and metabolic analysis of the parent tumor cells. The CSF EVs express key CNS tumor biomarkers and therapy targets undetectable in whole CSF and relay the brain tumor metabolic adaptations. Metabolic dependencies can represent potential therapy targets. The clinical implications of biomarker EV proteomic discovery represent a promising platform for diagnostic and prognostic purposes in brain solid tumors, a leading cause of cancer-related mortality at all ages.