Antiangiogenesis Treatment for Glioblastoma Multiforme: Challenges and Opportunities

Angiogenesis is a major hallmark of cancer cells, and glioblastomas are among the most angiogenic tumors. The cascade of angiogenesis is probably initiated by hypoxia, leading to the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Both VEGF and bFGF have paracrine effects on endothelial cells, pericytes, or both, causing the formation of hyperpermeable tumor blood vessels. Advanced MRI techniques, such as dynamic contrast-enhanced, dynamic susceptibility, and arterial spin labeling MRI, have provided semiquantitative measurements of tumor vascular permeability and perfusion. A decrease in vascular permeability and perfusion can be detected after antiangiogenesis drug treatment, either with monoclonal antibody such as bevacizumab that sequesters VEGF, or small-molecule VEGF receptor tyrosine kinase inhibitors. Therefore, antiangiogenesis therapies are being increasingly adopted for treating glioblastomas. However, caution must be exercised because neural stem cells are also sensitive to antiangiogenesis drugs and the combined effect of ionizing radiation. This article summarizes 30 years of laboratory and clinical research on glioblastoma angiogenesis and discusses its underlying biology, clinical trial results, vascular neuroimaging, and the potential side effects of antiangiogenesis treatment.

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Correspondence: Eric T. Wong, MD, Brain Tumor Center & Neuro-Oncology Unit, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: ewong@bidmc.harvard.edu

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