Angiogenesis in malignant primary and metastatic brain tumors

Patients with malignant primary and metastatic brain tumors have a poor prognosis, despite developments in diagnostic and therapeutic modalities. Therefore in the past decade a search for new therapeutic possibilities has started. The inhibition of angiogenesis, the sprouting of new capillaries from preexisting vasculature, which is an absolute requirement for the growth of tumors beyond a size of a few cubic millimeters, is one of the most promising approaches with which to influence tumor growth. This review focuses on the critical role of angiogenesis in the development of normal brain and the blood-brain barrier. We discuss the importance of angiogenesis in the formation of malignant brain tumors and in blood-brain barrier function in these tumors and possible consequences of altered blood-brain barrier properties for antiangiogenic therapy. Furthermore, results of current clinical trials with antiangiogenic drugs are reviewed, and clinical perspectives of antiangiogenic therapy in malignant brain tumors are outlined.