VEGF Manipulation in Glioblastoma

Glioblastoma is the most common malignant primary brain tumor that is universally lethal, despite optimized treatment including surgery, radiation, and chemotherapy. Targeting angiogenesis has been and continues to be an attractive therapeutic modality in both newly diagnosed and recurrent glioblastoma patients. Vascular endothelial growth factor (VEGF) is the most abundant and important mediator of angiogenesis in glioblastoma. Multiple strategies have been developed to target VEGF/VEGF receptor (VEGFR)-mediated angiogenesis, including VEGF blockade, VEGF Trap, and suppression of VEGFR signaling via receptor tyrosine kinase inhibitors (TKIs). These strategies have been explored in a spectrum of clinical trials, yielding findings that have all contributed to furthering our overall understanding of antiangiogenic therapy. The role of these agents and how to best incorporate them into the treatment paradigm for glioblastoma continues to evolve as understanding of resistance mechanisms improves. Although the excitement surrounding antiangiogenic therapy has waned over the years due to the lack of durable responses and survival benefit, there continues to be hope that combining antiangiogenic therapies with radiation therapy, cytotoxic drugs, immunotherapy, and targeted molecular agents may greatly enhance treatment strategies for high-grade gliomas.