Recent developments in the treatment of angiogenesis

Inhibitors of angiogenesis have considerable therapeutic potential for the treatment of malignant tumours which are angiogenesis-dependent, as well as for the treatment of specific angiogenic diseases, such as proliferative retinopathy. Recent work suggests that inhibitors fall into several categories. Those that inhibit in some manner the angiogenic factor, vascular endothelial growth factor (VEGF) either by disruption of VEGF receptor-mediated signal transduction (chemokines), or by preparation of soluble receptor molecules for VEGF which bind specifically to circulating VEGF without stimulating mitogenesis, thus inhibiting binding to receptors on the vascular endothelial cells themselves. Another method is the production of inhibitors of matrix metalloproteinases (MMPs) and specific integrins (alpha v beta(3)), which generally act in a similar manner to prevent vascular assembly. Particularly exciting is the recent description of a naturally-occurring anti-angiogenic peptide which is secreted by primary tumours and inhibits metastases, This protein, angiostatin, is able to induce dormancy in tumours with concurrent regression. The possibilities for therapy with this protein are very promising.