Between 1970 and 1994, cancer claimed the lives of about 500,000 Americans every year. According to the most recent statistics, it is estimated that 1.3 million new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. Amongst the leaders in the fight to reduce these figures are a number of inhibitors of angiogenesis. This therapeutic class is anticipated to represent a major focus of anti-cancer therapy (click here for "Cancer Treatment 2002" an analysis of future directions in cancer therapeutics) and indeed by 2006, the market for all products that play a role in angiogenesis is likely to reach $1.75 billion. This therapeutic class is also receiving growing attention as a strategy for treating retinal diseases and also inflammatory conditions such as rheumatoid arthritis. On the other hand molecules able to stimulate angiogenesis are gaining a place in the treatment of various ischemic diseases. Thrombolytic, antithrombotic and anticoagulant treatments represent the major acute therapeutic options for the treatment of myocardial infarction and peripheral arterial occlusive disease (click here for "Heart/ Cardiovascular Disease 2002" an analysis of future directions in cardiovascular therapeutics). However, in the days and weeks following myocardial damage, strategies to prevent further ischemic cell death or to promote the recovery of damaged tissue may be of greater advantage, particularly for patients with congestive heart failure. Stimulators of angiogenesis may help meet this clinical demand and in doing so this therapeutic class is expected to boost the market for modulators of angiogenesis by a further $650 million by 2006. The majority of angiogenesis-related molecules in advanced development are VEGF homologues, despite the physiological importance of VEGF and the risk of side effects following treatment with its homologues. As the angiogenesis field matures, other families related to angiogenesis are being identified and some of these may represent improved targets for the modification of vascularization. The angiopoietins comprise one such family of proteins that have pro or antiangiogenic activities. Through a proprietary technology designed to identify transcripts of all expressed genes, CuraGen researchers have recently isolated a cDNA encoding an angiopoietin-related protein designated angioarrestin. The mRNA expression profile of angioarrestin was striking in that it was down-regulated in many tumor tissues when compared with adjacent nontumor tissue. Furthermore, ectopic expression of angioarrestin in HT1080 tumor cells resulted in a marked reduction in their tumorigenic activity. This was related to blocks in critical processes involved in the angiogenic cascade, such as vascular endothelial growth factor/basic fibroblast growth factor-mediated endothelial cell proliferation, migration, tubular network formation, and adhesion to extracellular matrix proteins. These findings reveal a novel function for angioarrestin as an angiogenesis inhibitor and indicate that the molecule may be a potential cancer therapeutic. Since angiopoietins have been implicated in stroke and myocardial infarction, studies investigating the place that angioarrestin holds in this conditions are eagerly awaited.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk