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.