Ruchika Fnu, Suvarnapathaki Sanika, Serrano-Farias Antolin, Bettegowda Chetan, Rincon-Torroella Jordina
Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Brain Sci. 2025 May 28;15(6):585. doi: 10.3390/brainsci15060585.
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.
胶质母细胞瘤（GBM）是成人中最常见的原发性脑肿瘤，中位生存期为15至18个月。与所有肿瘤一样，GBM细胞表现出一种称为瓦伯格效应的代谢转变，即使在常氧条件下也倾向于糖酵解。葡萄糖转运蛋白1（GLUT1）是GBM细胞中的主要葡萄糖转运体，已发现其在这些细胞中过度表达。糖酵解产生的酸性微环境促进免疫逃逸、治疗抗性和肿瘤生长。GLUT1的过度表达由缺氧诱导因子-1α（HIF-1α）、c-Myc和其他与肿瘤侵袭性以及不良预后相关的途径驱动。最近的研究突出了靶向GBM中GLUT1的治疗潜力。临床前研究表明，GLUT1抑制剂，如WZB117和BAY-876，可有效损害肿瘤代谢、降低细胞活力并改善体外和动物模型中的生存期。GLUT1表达也可作为一种预后标志物，其水平升高与不良结局相关。本综述强调了GLUT1在GBM生物学中作为潜在治疗靶点和生物标志物的重要性。
