Longitudinal Monitoring of Glioblastoma Small Extracellular Vesicle Evolution Using a Nanodiagnostic to Detect Emergence of Glioma Stem Cells Driving Recurrent Disease

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Abstract Assessing therapeutic response in glioblastoma (GBM) is a major factor limiting the clinical development of new and effective therapies. The intracranial location limits serial biopsies, and only provides an intermittent view of the tumor molecular profile from the initial resection. Liquid biopsy techniques, specifically small extracellular vesicle (sEV) analysis, have the potential to overcome these limitations by providing a window into the brain using peripheral blood. To address the need for monitoring tumor evolution and therapeutic resistance, we developed a GBM biomarker panel (ATP1B2, EAAT2, CD24, CD44, CD133 and EGFR) for multiplexed profiling of sEVs using an advanced GBM Extracellular vesicle Monitoring Phenotypic Analyzer Chip (GEMPAC). We successfully tracked patient response to treatment by monitoring changes in glioma stem cell markers on circulating sEVs. We propose that these results provide a strong rationale for using GBM sEVs as a serial monitoring tool in the future clinical management of GBM patients.

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