Tumour vasculature as a target for anticancer therapy

The development of a blood supply is crucial to the growth and metastasis o f cancer: The factors involved in this are complex, however tumour hypoxia and macrophage infiltration are responsible for the synthesis of pro-angiog enic cytokines such as vascular endothelial growth factor (VEGF) and the fi broblast growth factors. These factors stimulate proliferation of vascular endothelial cells. the synthesis of proteases such as urokinase type plasmi nogen activator (uPA) and the matrix metalloproteases, which result in dige stion of the extracellular matrix and allow endothelial cell invasion. Endo thelial cell motility is promoted by binding of extracellular matrix protei ns such as vitronectin and fibronectin to integrins expressed on the plasma membrane of endothelial cells. Interfering with any of these steps may inh ibit the process of angiogenesis and drugs aimed at modulation of angiogene sis are currently undergoing evaluation in early clinical studies. This pap er reviews our current understanding of angiogenesis and how it may be used as a target for the treatment of cancer; (C) 2000 Harcourt Publishers Ltd.