The Role of Liquid Biopsy in Brain Tumors

Current methods of diagnosis and longitudinal monitoring of brain tumors stand to be supplemented and improved by liquid biopsy. Liquid biopsy is the testing of molecular biomarkers found in biofluids that give insight into a pathological state. This chapter gives a brief overview of glioma diagnosis and management in the context of the 2021 WHO classification of central nervous system (CNS) tumors and the role of liquid biopsy in that process. Although an overview of cell-free DNA and circulating tumor cells with respect to liquid biopsy is provided, this chapter focuses on extracellular vesicles (EVs) and their cargo in the context of liquid biopsy. Different EV-derived analytes including proteins, lipids, metabolites, DNA, mRNA, miRNA, lncRNA, and circRNA are described, and a comprehensive literature review of currently characterized metabolites and their potential implications as biomarkers for gliomas is evaluated. Several of the EV analyte assays reviewed here may be ready for clinical trials and adoption into clinical workflow. Additionally, this chapter explores challenges to EV-based liquid biopsy including EV isolation and characterization. Future directions are also highlighted, such as the characterization of EV subpopulations, the utilization of EVs for drug delivery, clinical trial endpoint determination, and diagnostic and therapeutic marker discovery.