Tumor angiogenesis and current therapeutic options for inhibition

The inhibition of angiogenesis provides a novel and unique opportunity to therapeutically target tumors. For the first time ever, cancer therapy is not directly attacking tumor cells themselves but targets the surrounding tumor microenvironment (stroma). Vascular endothelial growth factor (VEGF) is the most important tumor angiogenic factor. VEGF and VEGF receptor (VEGFR) neutralizing therapies either in combination with classical chemotherapy or as monotherapy are routinely used in clinical oncology. Anti-angiogenic drugs have within a few years dramatically influenced the field of systemic cancer therapy. However, their efficacy is limited and numerous fundamental questions relating to the mechanisms of tumor angiogenesis and the rational translational exploitation in the clinical treatment remain to be answered. This review provides an overview about the key molecular regulators of angiogenesis and the sequential cascade of angiogenic sprouting, vessel assembly and vessel maturation. Clinically approved anti-angiogenic drugs are reviewed and the status quo of ongoing preclinical angiogenic research on its way from bench to bedside is summarized.