Antiangiogenic Therapy of High-Grade Gliomas

Angiogenesis plays a critical pathologic role in malignant gliomas. In the past few years, numerous studies using bevacizumab (BEV), a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), have been conducted in patients with brain tumors. Current evidence suggests that such treatment produces favorable results in patients with recurrent glioblastoma multiforme (GBM), but is not associated with any benefits in newly diagnosed GBM and recurrent WHO grade III gliomas. Initial experience using BEV for management of central nervous system radiation necrosis demonstrated radiographic improvement in the majority of cases, but optimal dose and treatment duration in such cases still remain in question. The results of clinical trials on other antiangiogenic agents in patients with malignant gliomas were generally disappointing. Future therapeutic approaches should include strategies that targets different angiogenic pathways, block tumor invasiveness, and inhibit GBM stem cells. Evaluation of validated biomarkers and novel imaging parameters may eventually allow better selection of patients who will likely benefit from treatment with VEGF inhibitors.