Antiangiogenic strategies for the treatment of gliomas

Malignant gliomas (glioblastoma and anaplastic forms of astrocytoma and oligodendroglioma) are highly vascularized tumors and, therefore, constitute ideal targets for new antiangiogenic treatments. Angiogenesis is a highly complex biologic process, involving a multitude of different molecular drivers and signaling pathways. The vascular endothelial growth factor (VEGF) pathways appear to play a key role in this process, and targeting such pathways has emerged as one of the most efficient antiangiogenic strategies. To date, the best studied of these drugs has been the anti-VEGF monoclonal antibody, bevacizumab. In recurrent malignant gliomas, this drug achieves high response rates and seems to prolong progression-free survival. However, similar to other solid tumors, the magnitude of the survival benefit has been less obvious, as most patients eventually progress after an initial clinical benefit. In this chapter, we seek to recapitulate the development of antiangiogenesis treatment for malignant gliomas, from molecular mechanisms to challenges in the evaluation of antiangiogenic drugs in the clinical setting.