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Researchers Find Possible New Route to Making Cancer Cells Vulnerable

DURHAM, N.C. -- Researchers at the Howard Hughes Medical Institute at Duke University Medical Center have shown how drugs that stop organ transplant rejection also partially reverse drug resistance in certain cancer cells.

Such resistance, which thwarts cancer chemotherapy, is a principal cause of death for cancer patients. The scientists have identified a new target to stop drug resistance in cancer cells. The researchers believe the finding will help scientists develop new compounds to prevent drug resistance in patients with cancer, but without compromising the immune system.

"We may have identified an Achilles' heel in the body's natural reaction in expelling toxic drugs," said geneticist Dr. Joseph Heitman, the study's principal investigator.

The research was supported in part by the National Institute of Environmental Health Sciences and a Rhone Poulenc Rorer Hematology Scholar award to colleague Dr. Charles Hemenway.

Heitman and Hemenway, both researchers in Duke's Comprehensive Cancer Center, reported their findings in the Aug. 2 issue of the Journal of Biological Chemistry. They found that three drugs given to stop organ transplant rejection -- cyclosporin, FK506, and rapamycin -- also block the cellular pump that expels cancer chemotherapy drugs. But it turns out the drugs block the pump by different mechanisms.

Previously, scientists believed the anti-rejection drugs acted like sludge in a gas tank, clogging the pump mechanism. But the Duke scientists showed that FK506 and rapamycin also tie up a separate protein, called FKBP12, which they showed is an essential activator for the pump to work correctly. In other words, the two drugs primarily halt the cellular pump by removing a vital part, like a valve from a car's fuel pump.

"Cyclosporin-related drugs are now being tested for their ability to reverse chemotherapy resistance in cancer patients, but little
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Contact: Karyn Hede George
georg016@mc.duke.edu
919-660-1301
Duke University
2-Aug-1996


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