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New cause of tamoxifen resistance in breast cancer cells discovered at Lombardi

When a woman receives a breast cancer diagnosis her entire life may change in the blink of an eye. But the nature of that change is governed by the smallest alterations that take place within the proteins of the tumor cells, determining what treatments she can pursue with a hope of cure and those to which her cancer is resistant.

Scientists from the Lombardi Comprehensive Cancer Center announced today the discovery of a new mechanism of resistance to endocrine or anti-hormonal therapies, such as Tamoxifen and Faslodex. This research may allow oncologists to screen women for responsiveness to these treatments, and provides a much-needed clue to reversing resistance. The research, led by Robert Clarke, PhD, DSc, a professor of oncology and of physiology and biophysics at Georgetown University Medical Center, indicates that a gene previously thought to be unrelated to breast cancer may be responsible for some resistance to endocrine therapy.

The gene, called human X-box binding protein-1 (XBP1), is an alternatively spliced transcription factor that participates in a stress-signaling pathway to protect cells from damage. In a paper published online in the Journal of the Federation of American Societies for Experimental Biology (FASEBJ) on July 27, Clarke and his colleagues at the Lombardi Comprehensive Cancer Center (part of Georgetown University Medical Center) found that over-expression of the spliced variant of the gene in estrogen receptor-positive breast cancer cells led to reduced sensitivity to Tamoxifen and Faslodex.

According to Lombardi medical oncologist Minetta Liu, MD, it is expected that all hormone receptor positive metastatic breast cancers will eventually develop resistance to endocrine therapies. When this happens, doctors must switch their patients to a different class of drugs throwing their lives into limbo once again as treatment schedules are changed and new side effects develop.

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Contact: Becky Wexler
rjw43@georgetown.edu
202-687-5100
Georgetown University Medical Center
10-Aug-2007


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