Circulating biomarkers for gliomas

Currently, gliomas are diagnosed by neuroimaging, and refined diagnosis requires resection or biopsy to obtain tumour tissue for histopathological classification and grading. Blood-derived biomarkers, therefore, would be useful as minimally invasive markers that could support diagnosis and enable monitoring of tumour growth and response to treatment. Such circulating biomarkers could distinguish true progression from therapy-associated changes such as radiation necrosis, and help evaluate the persistence or disappearance of a therapeutic target, such as an oncoprotein or a targetable gene mutation, after targeted therapy. Unlike for other tumours, circulating biomarkers for gliomas are still being defined and are not yet in use in clinical practice. Circulating tumour DNA (ctDNA) isolated from plasma has been shown to reflect the mutational status of glioblastoma, and extracellular vesicles (EVs) containing ctDNA, microRNA and proteins function as rapidly adapting reservoirs for glioma biomarkers such as typical DNA mutations, regulatory microRNAs and oncoproteins. Ideally, circulating tumour cells could enable profiling of the whole-tumour genome, but they are difficult to detect and can reflect only a single cell type of the heterogeneous tumour composition, whereas EVs reflect the complex heterogeneity of the whole tumour, as well as its adaptations to therapy. Although all categories of potential blood-derived biomarkers need to be developed further, findings from other tumour types suggest that EVs are the most promising biomarkers.