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Restoring tamoxifen sensitivity in resistant breast cancer cells

The widely used breast cancer drug tamoxifen (Nolvadex®), which can become less effective over time, might retain its full strength indefinitely if used along with a second drug, according to new research in mice conducted by investigators from the National Cancer Institute (NCI), part of the National Institutes of Health, and their partners. The results appear in the December 11, 2006, issue of Cancer Cell*.

Tamoxifen has been used successfully since the 1970s to treat certain types of breast cancer and to prevent them from recurring after surgery. Clinicians observed that tamoxifen treatment initially reduced the rate of recurrence by nearly 50 percent. Over time, however, patients develop resistance to the drug and tamoxifen loses its effectiveness as a cancer treatment.

"Tamoxifen has been extremely important in the management of breast cancer," said NCI Director John E. Niederhuber, M.D. "Being able to overcome resistance would be an important advance."

In the study, the research team, led by William Farrar, Ph.D., of NCI's Center for Cancer Research at Frederick, Md., found that the effectiveness of tamoxifen in cell cultures and in mice can be fully restored by the use of a compound called disulfide benzamide, or DIBA. The investigators confirmed their study hypothesis about DIBA's effect on tamoxifen resistance by using the compound in mice that were engineered to have tamoxifen-resistant tumors and saw that tumor growth was reduced by nearly 50 percent when DIBA was administered.

"Exposure to DIBA causes certain physical changes to occur between the estrogen receptor and the biological machinery that stimulates cell division. By coincidence, these changes also restore the estrogen receptor to a form that makes it vulnerable once again to tamoxifen," said Li Hua Wang, Ph.D., lead author of the study.

Some, but not all, breast cancer cells have specific receptors that bind estrogen molecules circulating in the bloods
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Source:SAIC-Frederick, Inc.


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