New cause of Tamoxifen resistance is found

Aug 13, 2007

U.S. scientists have discovered a new mechanism for resistance to Tamoxifen and Faslodex endocrine or anti-hormonal breast cancer therapies.

The researchers at the Lombardi Comprehensive Cancer Center at the Georgetown University Medical Center said their findings might allow oncologists to screen women for responsiveness to such treatments, and provide clues to reversing resistance.

The research, led by Professor Robert Clarke, indicates a gene -- X-box binding protein-1, or XBP1 -- previously thought to be unrelated to breast cancer might be responsible for some resistance to endocrine therapy.

The researchers said the gene is an alternatively spliced transcription factor that participates in a stress-signaling pathway to protect cells from damage. Clarke and his colleagues determined over-expression of the spliced variant of the gene in estrogen receptor-positive breast cancer cells led to reduced sensitivity to Tamoxifen and Faslodex.

The study was published online in the July 27 issue of the Journal of the Federation of American Societies for Experimental Biology.

Copyright 2007 by United Press International

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