Mode of action and clinical impact of VEGF signaling inhibitors.

The established role of VEGF signaling in promoting tumor angiogenesis has led to the development and clinical validation of several agents that selectively target this pathway in patients with advanced-stage malignancies. These include neutralizing anti-VEGF monoclonal antibodies, soluble VEGF receptors and small-molecule inhibitors of VEGF receptor function, administered either as monotherapy or in combination with chemotherapy. Several modes of action have been identified, such as inhibition of new vessel growth, regression of newly formed vasculature, alteration of tumor vessel function and direct effects on tumor cells. VEGF-targeting drugs currently play an important role in the treatment of cancer and their impact will probably further increase in the future.