Current Status and Future Perspectives of Anti-Angiogenic Therapeutic Attempts for Glioblastoma

Abstract

Glioblastoma, the most aggressive brain tumor, is associated with invariably poor prognosis in spite of extensive surgical resection, radiotherapy, and concomitant and adjuvant chemotherapy. The histological landmarks of glioblastoma are massive necrosis and prominent angiogenesis. Glioblastoma vasculature is structurally and function-ally aberrant, characterized by tortuous and leaky vessels, with an increased diameter and significantly thickened basement membranes. This altered vasculature enhances tumor hypoxia and affects the possibility of effective drug delivery to the tumor. Many efforts have been spent in developing therapeutic strategies targeting glioblastoma neo-angiogen-esis, with the dual aim of inhibiting tumor growth and stabilizing tumor vasculature, therefore improving chemotherapy delivery to the tumor. Bevacizumab, a humanized monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF), has been approved by Food and Drug Administration (FDA) for recurrent glioblastoma, but unfortunately it seems to have limited efficacy in terms of overall survival. Here, we review literature data both from molecular and clinical studies and analyze the state of the art and the future perspectives of antiangiogenic therapies for glioblastoma.