Cancer Drug Gleevec Could Fight Stroke

By Ed Edelson
HealthDay Reporter
Tuesday, June 24, 2008; 3:00 AM

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MONDAY, June 23 (HealthDay News) -- A powerful weapon against cancer might also boost stroke patients' survival, new research suggests.

Gleevec, long hailed as a "wonder drug" against cancers such as chronic myelogenous leukemia (CML), will be tested to see if it can boost the effectiveness and limit the side effects of the clot-dissolving drug tissue plasminogen activator (tPA), an international team of researchers say.

One of the ways that Gleevec stops the growth of cancer cells is to block receptors of platelet-derived growth factor-CC (PDGF-CC), explained Daniel Lawrence, professor of cardiovascular medicine at the University of Michigan and a member of the research team.

Studies performed at his lab, as well as at Sweden's Karolinska Institute, have both shown that blocking those receptors improves the activity of tPA.

Doctors typically give tPA in the hours after an ischemic stroke, which occurs when a blood clot blocks a brain artery. About 80 percent of all strokes are ischemic, and tPA is given to dissolve the clots.

But there's a big downside with the drug: It also can increase the odds for brain hemorrhage.

Reporting in the June 22 online edition of the journal Nature Medicine, the researchers at Karolinska and in Michigan showed for the first time that tPA increases the risk of bleeding by acting on PDGF-CC, as well as the cellular receptor to which it binds. This activity makes blood vessels in the brain dangerously leaky.

However, in other laboratory tests and in animal studies, Gleevec prevented this leakiness by blocking PDGF-CC receptors.

"Blocking the receptor reduces formation of edema -- swelling of the brain -- and so even in the absence of tPA, the [Gleevec] treatment would be beneficial," Lawrence pointed out.

But Gleevec might also extend tPA's usefulness, he added. "tPA loses its efficacy three hours after a stroke. Part of that loss may be an increase in major side effects, and the major side effect of tPA is bleeding," Lawrence explained. "You could conceivably block the receptor and give tPA beyond its current three-hour limit and still be effective at removing the blockage of a brain artery but reduce the complications."