May 9, 2003 A discovery from the University of Illinois at Chicago College of Pharmacy may make it possible to anticipate which breast cancer patients will respond to tamoxifen and to devise a more appropriate therapy for those who do not.
Tamoxifen has been used for more than 25 years to treat patients with certain types of breast cancer. But the drug is not effective for all patients, and until now, doctors and researchers have been unable to predict who would benefit and why.
In an article in the current issue of the British Journal of Cancer, Debra Tonetti, assistant professor of biopharmaceutical sciences in the UIC College of Pharmacy, reports the results of a study that identifies a possible predictor of tamoxifen resistance.
Tamoxifen works by blocking the effect of estrogen, which promotes the growth of breast cancer cells containing the estrogen receptor. However, in a retrospective study, Tonetti found that patients whose disease recurred had high levels of an enzyme called protein kinase C alpha, whereas patients who remained disease-free for at least five years had very low levels of PKC-alpha or none at all.
"Overproduction of PKC-alpha may be used to predict who will not respond to tamoxifen," Tonetti said. "In addition, we found that in mice, tumors that overproduce PKC-alpha completely regress with estrogen treatment."
These findings, her paper states, "may have important therapeutic applications in the management of breast cancer patients."
The initial study used archival biopsied tissue from 30 patients. Tonetti is now expanding her study, funded in part by the National Cancer Institute, and will use tissue from several hundred patients matched by age and disease stage to substantiate the preliminary findings. Upon completion of the entire study, in about 18 months, she hopes to start clinical trials.
"Cancer recurrence is a real problem," she said. "Finding more effective strategies for treating it would be very helpful."
For more information on the UIC College of Pharmacy, visit http://www.uic.edu/pharmacy.
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