Angiogenesis in Malignant Gliomas and Bevacizumab Resistance

Abstract

Standard therapy for malignant gliomas includes maximal resection followed by radiotherapy and temozolomide. The increase in neovascularization in high-grade gliomas serves the increased metabolic demands of these fast-growing tumors and the main pathway mediating this process involves vascular endothelial growth factor (VEGF) and its receptor. This pathway is targeted by bevacizumab (BEV), an anti-VEGF monoclonal antibody. Though preclinical trials with BEV were promising, clinical trials failed to show improvement in overall survival, and ultimately GBM become resistant to BEV. By better understanding the molecular mechanisms involved in angiogenesis, new targets may be identified and by elucidating the mechanism behind BEV resistance, new treatment modalities may be developed to treat these aggressive tumors.