Glioblastoma (GBM) is the most common
primary brain tumor occurring in America. Despite recent advances in
therapeutics, the prognosis for patients with newly diagnosed GBM remains dismal. As these
tumors characteristically show evidence of angiogenesis (neovascularization) there has been great interest in developing anti-angiogenic therapeutic strategies for the treatment of patients with this disease and some anti-angiogenic agents have now been used for the treatment of patients with
malignant glioma tumors. Although the results of these clinical trials are promising in that they indicate an initial therapeutic response, the anti-angiogenic
therapies tested to date have not changed the overall survival of patients with
malignant glioma tumors. This is due, in large part, to the development of resistance to these
therapies. Ongoing research into key features of the neovasculature in
malignant glioma tumors, as well as the general angiogenesis process, is suggesting additional molecules that may be targeted and an improved response when both the neovasculature and the
tumor cells are targeted. Prevention of the development of resistance may require the development of anti-angiogenic strategies that induce apoptosis or cell death of the neovasculature, as well as an improved understanding of the potential roles of circulating endothelial progenitor cells and vascular co-option by
tumor cells, in the development of resistance.