VEGF Receptor Signaling in Tumor Angiogenesis

The growth of human tumors and development of metastases depend on the de novo formation of blood vessels. The formation of new blood vessels is tightly regulated by specific growth factors that target receptor tyrosine kinases (RTKs). Vascular endothelial growth factor (VEGF) and the Flk-1/KDR RTK have been implicated as the key endothelial cell-specific factor signaling pathway required for pathological angiogenesis, including tumor neovascularization. Inhibition of the VEGF tyrosine kinase signaling pathway blocks new blood vessel formation in growing tumors, leading to stasis or regression of tumor growth. Advances in understanding the biology of angiogenesis have led to the development of several therapeutic modalities for the inhibition of the VEGF tyrosine kinase signaling pathway. A number of these modalities are under investigation in clinical studies to evaluate their potential to treat human cancers.