Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms

Background: Glioblastoma multiforme (GBM) has a very poor prognosis and novel treatment strategies are urgently needed. GBM appears to be an optimal target for anti-angiogenic therapy as the tumour shows a high degree of endothelial cell proliferation and pro-angiogenic growth factor expression. Objective: To examine the role of angiogenic factors (particularly VEGF) in glioma and whether inhibition of these factors can be used as a treatment. Methods: A review of relevant literature. Results/conclusions: Anti-angiogenic therapy has fulfilled the proof of concept in glioma animal models. In glioma patients, the efficacy of anti-angiogenic mono-therapies initially has been disappointing. However recent clinical trials combining bevacizumab, an anti-VEGF antibody, with chemotherapy reported very encouraging response rates. Although randomized phase III clinical trials with anti-angiogenic molecules are not yet available for GBM patients, this treatment regimen is already applied off protocol in several clinical centers. It should be kept in mind though that tumours can develop escape mechanisms. In particular invasive cells, which migrate away from the highly vascularized tumour core, are not targeted by anti-angiogenic therapies. In our opinion, the future of anti-angiogenic therapy will rely on a combination strategy including chemotherapy and drugs that target invasive glioma cells.