Kinetics of vascular normalisation by VEGFR2 blockade governs brain tumour response to radiation: role of angiopoietin-1 and matrix metalloproteinases

Background: A recent successful Phase III clinical trial using a VEGF-specific antibody suggests that antiangiogenic therapy must be combined with cytotoxic therapy for the treatment of solid tumors. However, there are no guidelines for optimal scheduling of these therapies. Specifically, Glioblastoma Multiforme is characterized by a dilated, tortuous, disorganized, and leaky vasculature and by high levels of VEGF. These abnormalities may impair the delivery of oxygen and therapeutics. Methods: Using human glioma xenografts implanted under cranial windows in nude mice, we investigated the mechanism and kinetics…