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. VEGF binds to a number of receptors, including VEGFR-1 and VEGFR-2, and the interactions with these receptors and the signaling pathways that mediate angiogenesis are only now being delineated. PlGF has recently been shown to synergize with VEGF in the response to angiogenesis, although the mechanisms are still the subject of intense investigation and not fully understood. It may be advantageous to target PlGF rather than VEGF since the expression of receptors for the former is largely restricted to pathological conditions thus allowing for improved specificity. Consequently PlGF modulation is receiving considerable interest from the cutting edge cardiovascular biotech, ThromboGenics Ltd. LeadDiscovery has recently produced a series of dossiers highlighting the ThromboGenics pipeline (click here for access) and two of these dossiers featured the company's advances in the development of PlGF-related targets. Now the company has published a breakthrough article in Nature Medicine reporting that PlGF stimulated angiogenesis and collateral growth in ischemic heart and limb with at least a comparable efficiency to VEGF. Furthermore, an antibody against Flt1, a receptor for PlGF, suppressed neovascularization in tumors and ischemic retina, and angiogenesis and inflammatory joint destruction in autoimmune arthritis. Anti-Flt1 also reduced atherosclerotic plaque growth and vulnerability, although the atheroprotective effect was not attributable to reduced plaque neovascularization. Inhibition of VEGF receptor Flk1 did not affect arthritis or atherosclerosis, indicating that inhibition of Flk1-driven angiogenesis alone was not sufficient to halt disease progression. The anti-inflammatory effects of anti-Flt1 were attributable to reduced mobilization of bone marrow derived myeloid progenitors into the peripheral blood; impaired infiltration of Flt1-expressing leukocytes in inflamed tissues; and defective activation of myeloid cells. Thus, PlGF and Flt1 constitute potential candidates for therapeutic modulation of angiogenesis and inflammation and ThromboGenics field-leading position in this area is expected to drive a variety of therapeutic areas forward. The company is actively seeking interested pharmaceutical partners who may be able to optimize this process.

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