Vascular endothelial growth factor signaling pathways: therapeutic perspective.

The establishment of a vascular supply is one of the earliest and most important events occurring during embryonic development. Growth and maturation of a functional vascular network are complex and still incompletely understood processes involving orchestrated activation of vascular progenitors in the early stages of embryonic development followed by vasculogenesis and angiogenesis. These processes require a tightly regulated activation of several growth factors and their receptors. The role of vascular endothelial growth factors (VEGF) and their receptors has been studied extensively due to their prominent role during blood vessel formation. Mice deficient in various VEGF ligands or receptors show serious defects in vascular formation and maturation. Moreover, members of the VEGF family are involved in other significant biological processes, including lymphangiogenesis, vascular permeability, and hematopoiesis. Importantly, VEGF is released by tumor cells and induces tumor neovascularization. It is now well established that the VEGF axis represents an important target for antitumor therapy. Aberrant VEGF signaling is also a feature of several other pathologic conditions, such as age-related macular degeneration and rheumatoid arthritis.