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Mass. General team identifies new class of antiangiogenesis drugs
Date:7/1/2011

Massachusetts General Hospital (MGH) researchers have discovered the first of an entirely new class of antiangiogenesis drugs agents that interfere with the development of blood vessels. In a report in Proceedings of the National Academy of Sciences/Early Edition, the investigators describe how a compound derived from a South American tree was able, through a novel mechanism, to interfere with blood vessel formation in animal models of normal development, wound healing and tumor growth.

"Most of the FDA-approved antiangiogenesis drugs inhibit the pathway controlled by vascular endothelial growth factor or VEGF, which directly stimulates blood vessel development," says Igor Garkavtsev, MD, PhD, of the Steele Laboratory for Tumor Biology at MGH, lead author of the study. "Although these drugs have become standard treatments for several types of cancer, they only provide modest benefit in terms of extending patient survival, so more effective drugs targeting tumor vasculature are needed."

While tumors need to generate and maintain their own blood supply to keep growing, tumor vasculature tends to be highly disorganized, which interferes with the effectiveness of traditional treatments like radiation and chemotherapy. Drugs that target the VEGF pathway can "normalize" tumor vasculature and improve the effectiveness of other therapies, but in addition to their limited effect on patient survival, such agents also can generate resistance or have toxic effects.

In their search for drugs that block blood vessel growth in different ways, Garkavtsev and his colleagues focused on pathways involved with the adhesion of endothelial cells that line blood vessels to the outer vessel wall. Appropriate cellular adhesion is essential to blood vessel function, and cells lining the tangled vessels characteristic of tumors often exhibit altered adhesion. Using a novel two-step strategy, the team first screened 50,000 compounds to find those
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2765
Massachusetts General Hospital
Source:Eurekalert

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