GLUT1 as a Potential Therapeutic Target in Glioblastoma

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults, with a median survival of 15–18 months. GBM cells, like all tumors, exhibit a metabolic shift known as the Warburg effect, favoring glycolysis even under normoxic conditions. GLUT1 is a primary glucose transporter in GBM cells and has been found to be overexpressed in these cells. The acidic microenvironment created by glycolysis facilitates immune evasion, therapy resistance, and tumor growth. Overexpression of GLUT1 is driven by hypoxia-inducible factor-1α (HIF-1α), c-Myc, and other pathways which have been correlated with tumor aggressiveness as well as poor prognosis Recent studies have highlighted the therapeutic potential of targeting GLUT1 in GBM. Preclinical research shows that GLUT1 inhibitors, such as WZB117 and BAY-876, effectively impair tumor metabolism, reduce cell viability, and improve survival in vitro and in animal models. GLUT1 expression also serves as a prognostic marker, with elevated levels linked to poor outcomes. This review highlights the importance of GLUT1 in GBM biology as a potential therapeutic target and biomarker.