Antiangiogenesis Treatment for Glioblastoma Multiforme: Challenges and Opportunities

Abstract

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.

Evaluation of Microvascular Permeability with Dynamic Contrast-Enhanced MRI for the Differentiation of Primary CNS Lymphoma and Glioblastoma: Radiologic-Pathologic Correlation

“…14,[28][29][30] These results may be explained by the differences in neovascularization, which is a hallmark in GB, 31 however, an unusual feature in (non-AIDS-related) PCNSL. 32 Thus, the microvascular blood flow to the tumor tissue in GB is often hampered by an abnormal tumor vasculature due to neovascularization comprising immature or defective endothelium, tortuosity, and thrombosis.…”

MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials

“…Many studies have emerged in recent years attempting to validate MR imagingbased perfusion imaging as a biomarker of angiogenesis (Online Table 2). [33][34][35][36][37][38][39][40][41] MR imaging can provide information on tumor perfusion by tracking a bolus of an exogenously administered contrast agent or by tracking endogenous magnetically labeled flowing blood. The former includes DCE PWI, which measures the T1 shortening effect of the contrast agent, and DSC PWI, which measures the susceptibility effect of the contrast agent on T2* GRE images.…”

Novel technologies for antiangiogenic drug delivery in the brain

“…[84][85][86] Many angiogenesis inhibitors, including those recently discovered, are limited when their clinical potential is considered. There is, therefore, an increased need for the novel approaches offered by nanotechnology and polymer chemistry.…”