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

inutes and it contributes to tumor survival."

The cPLA2 enzyme is known to regulate the levels of at last three molecules that promote tumor angiogenesis (the creation of new blood vessel networks to feed cancer cells).

The researchers set out to learn if they could enhance the effect of radiation therapy for lung and brain cancers by inhibiting this enzyme.

The idea was to implant tumors into normal mice and into mice that had been genetically engineered to be unable to produce cPLA2 and then compare the effect of radiation therapy on tumor progression in each.

The immense power of cPLA2 became apparent to Hallahan when a graduate student complained that her experiment failed because she could not grow tumors in mice that lacked the gene that produces cPLA2.

"While implanted tumors progressed as expected in normal mice used in the experiment, they were virtually undetectable in cPLA2 deficient mice," Hallahan says. "The 'failed experiment' was actually a significant discovery of the enormous control cPLA2 has in regulating tumor angiogenesis."

The scientists then examined the blood vessels of the cPLA2 deficient mice. While the blood vessels of cPLA2 deficient mice appeared normal, close inspection revealed the absence of a certain type of contractile cell that regulates blood flow.

"Without these cells, blood vessels can still grow into the tumor but blood cannot flow to the tumor," Hallahan says. "Cancer cannot survive without blood flow to feed it."

The central role of cPLA2 in determining the presence or absence of these contractile cells makes it a prime target for interventional therapy.

"Drugs that target cPLA2 have enormous potential for improving the success of radiation against highly angiogenic tumors," Hallahan says.

Hallahan has already identified an existing drug that inhibits cPLA2. It is a compound originally developed by Wyeth, now part of Pfizer, as a treatme
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Contact: Joni Westerhouse
westerhousej@wustl.edu
314-286-0120
Washington University in St. Louis
Source:Eurekalert

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