Anti-angiogenic strategies in glioblastoma

Introduction. - Glioblastoma, a highly angiogenic tumor, has poor prognosis despite aggressive conventional therapies combining surgery, chemotherapy and radiotherapy. Antiangiogenic strategies that have recently come to the clinic, are the most promising therapeutic approaches for these tumors. State of art. - Tumor hypoxia is the main trigger of angiogenesis processes driven primarily by vascular endothelial growth factor (VEGF). Clinical data indicate that inhibitors of VEGF such as bevacizumab or VEGF receptors such as tyrosine kinase inhibitors are of potential interest in the treatment of recurrent glioblastoma, with an acceptable toxicity. However, despite high rate of initial radiological response and rapid clinical improvement in about half of patients, therapeutic failure is the rule. Mechanisms of resistance remain poorly understood but an invasive phenotype and alternative angiogenesis factors may contribute to tumor escape. Conclusions and perspectives. - Anti-angiogenic strategies already play an important role in the management of recurrent glioblastoma. However, optimal combination and schedules of angiogenic inhibitors with radiotherapy and chemotherapy remain to be established. Important randomized clinical trials currently investigate therapeutic combinations for newly diagnosed glioblastoma. (C) 2011 Elsevier Masson SAS. All rights reserved.