Endothelial growth factor receptors in angiogenesis

Abstract

It is hard to underestimate the role of endothelial growth factor receptors in the generation of new blood vessels. This axis is involved in vascular development in embryos and angiogenesis in adults. As the signaling of these tyrosine kinase receptors has been elucidated, we have gained an appreciation of the complex interactions with other receptors, co-receptors, and downstream pathways. Its involvement in pathology makes it a particularly tempting therapeutic target with its manipulation offering several theoretical benefits. The most intensely studied is the role of anti-VEGFR drugs in cancer chemotherapy. Initial trials were disappointing but a decade ago the first drug targeting the vascular endothelial growth factor (VEGF) axis was approved, providing a vital proof of concept. Therapies specifically targeting the receptor are in early development for prevention of neovascular diseases of the eye. Conversely, promotion of revascularization following vascular occlusion is another possible application being studied. While these therapies show promise, the manipulation of VEGF receptors themselves remains a relatively small niche in the therapeutic armory. A deeper understanding of the receptor, its co-receptors, and the downstream web of signaling is required to complete the pieces of the puzzle and unlock the potential of this receptor pathway.