Tumour vasculature as a target for anticancer therapy.

The development of a blood supply is crucial to the growth and metastasis of cancer. The factors involved in this are complex, however tumour hypoxia and macrophage infiltration are responsible for the synthesis of pro-angiogenic cytokines such as vascular endothelial growth factor (VEGF) and the fibroblast growth factors. These factors stimulate proliferation of vascular endothelial cells, the synthesis of proteases such as urokinase type plasminogen activator (uPA) and the matrix metalloproteases, which result in digestion of the extracellular matrix and allow endothelial cell invasion. Endothelial cell motility is promoted by binding of extracellular matrix proteins such as vitronectin and fibronectin to integrins expressed on the plasma membrane of endothelial cells. Interfering with any of these steps may inhibit the process of angiogenesis and drugs aimed at modulation of angiogenesis are currently undergoing evaluation in early clinical studies. This paper reviews our current understanding of angiogenesis and how it may be used as a target for the treatment of cancer. Copyright 2000 Harcourt Publishers Ltd.