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Novel target for existing drug may improve success of radiation therapy
Date:9/16/2010

Scientists at Washington University School of Medicine in St. Louis have discovered a new drug target that could improve the effectiveness of radiation for hard-to-treat cancers.

The finding, published in the Journal of the National Cancer Institute, focuses on the role of the enzyme cytosolic phospholipase A2 (cPLA2). This enzyme promotes development and functioning of blood vessel networks that feed malignant tumors, enabling them to overcome the effects of radiation.

They have also identified a drug that stops production of the enzyme. Inhibiting the enzyme can stop the flow of blood tumors need to survive.

Cancers thrive and spread thanks to a unique ability to recruit networks of new blood vessels that penetrate into tumors, bringing oxygen and nutrients and potentially transporting cancer cells to other parts of the body.

Cancer cells start the process of new blood vessel construction, called angiogenesis, by releasing specific molecules into surrounding normal tissue, kicking off a cascade of molecular signals that cause cells lining existing blood vessels to divide and create new vessels. These new vessel networks link the tumor to the circulatory system and its life-sustaining cargo.

Lung cancer and glioblastoma, the most common type of primary brain tumor, are particularly adept at inducing new blood vessel creation via angiogenesis. They are also highly resistant to treatment by radiation.

"Our original objective was to measure the signaling molecules that enable lung and brain cancer to be resistant to radiation," says Dennis Hallahan, MD, the Elizabeth H. and James S. McDonnell III Distinguished Professor in Medicine and chair of the Department of Radiation Oncology at the School of Medicine and senior author of the study.

"There are hundreds of signaling molecules, but the enzyme cPLA2 stood out," Hallahan says. "Radiation of tumor cells triggers production of cPLA2 within two m
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Contact: Joni Westerhouse
westerhousej@wustl.edu
314-286-0120
Washington University in St. Louis
Source:Eurekalert

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