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
'"/>
Contact: Karyn Hede George
georg016@mc.duke.edu
919-660-1301
Duke University
2-Aug-1996