Section Review Oncologic, Endocrine & Metabolic: Angiogenesis inhibition as a drug target for disease: an update

Abstract

Angiogenesis is required for the development of many proliferative diseases, including granulomatous disease, such as rheumatoid arthritis, psoriasis and neoplasia, as well as diabetic retinopathy. A substantial effort is being made to develop inhibitors of angiogenesis for the treatment of these diseases. This article is an update of a previous review [Colville-Nash & Seed, Curr. Opin. Invest. Drugs (1993) 2:763-813], and reviews the recent developments in the use of: angiostatic steroids, fumagillol derivatives, somatostatin analogues, matrix metalloproteinase (MMP) inhibitors, modulators of vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), angiostatin, endostatin, platelet factor-4 (PF4), thrombospondin-1 (TSP-1), cell adhesion molecules (integrins and selectins), urokinase plasminogen receptor antagonists, cyclo-oxygenase (COX) and non-steroidal anti-inflammatory drugs (NSAIDs), nitric oxide synthase (NOS), cytokine-suppressing anti-inflammatory drugs (CSAIDs), and drug combinations. Most of these approaches have been shown to be effective in inhibiting tumour growth in vivo, and many in models of inflammation. The field has, therefore, a very wide range of effective drug targets which are being exploited. Many areas are still limited by their reliance on high molecular weight molecular technologies, antibodies and constructs; however, low molecular weight compounds are now being sought in areas such as cytokine suppression, VEGF, MMPs, COX, NOS, and adhesion molecules. Angiostatic therapy is a rapidly advancing, therapeutically viable and exciting field.