Neovascularization in Glioblastoma: Current Pitfall in Anti-angiogenic therapy

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. However, the survival of patients with GBM has been dismal after multi-disciplinary treatment with surgery, radiotherapy, and chemotherapy. In the efforts to improve clinical outcome, anti-angiogenic therapy with bevacizumab (Avastin) was introduced to inhibit vascular endothelial growth factor (VEGF) mediated tumor neovascularization. Unfortunately, the results from clinical trials have not lived up to the initial expectations. Patients either fail to respond to anti-angiogenic therapy or develop resistance following an initial response. The failure of anti-angiogenic therapy has led to a frustration among physicians and research community. Recent evidence indicates that the dogma of tumor neovascularization solely dependent on VEGF pathway to be overly simplistic. A realistic model of tumor neovascularization should include alternative pathways that are independent of VEGF signaling. A better understanding of the underlying processes in tumor neovascularization would help in designing successful anti-angiogenic treatment strategies.