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Breast cancer drug fulvestrant appears more effective in the presence of CK8 and CK18
Date:3/10/2010

s estrogen's effects.

Although fulvestrant has been used to treat cancer since the late 1980s, and is now commonly prescribed as a second-line defense against metastatic cancer cells, how the drug works is still not completely understood. Nephew said one of the aims of the research is to clarify fulvestrant's biochemistry, and understand why cancer cells eventually become unresponsive to the drug.

Second-line breast cancer therapies are employed when first-line approaches (tamoxifen, for example) don't work or stop working.

After conducting analyses of different cell lines and assaying gene and protein activity, Nephew, Xinghua Long (now a faculty member at Jiangnan University), and Meiyun Fan (now an assistant professor at the University of Tennessee-Memphis) believe they are able to present a compelling model for fulvestrant's action. The scientists believe that when fulvestrant encounters ER-alpha and binds to the receptor, the receptor forms a two-protein complex either with another ER-alpha -- or with ER-beta, a related but different estrogen receptor. The alpha-alpha or alpha-beta "dimer" is then removed to the nuclear matrix, where it binds to CK8 and CK18. It's the binding of ER-alpha to the nuclear matrix that would seem to signal protein-killing proteases to destroy ER-alpha. As the number of available estrogen receptors plummets, the connection between estrogen and cancer-related gene activity is weakened, and estrogen can no longer contribute to the growth of cancer cells.

Because many drug treatments can have a severely negative impact on quality of life, Nephew said fulvestrant and other cancer drugs should only be prescribed when their use is associated with a reasonable chance of successful outcomes. However, compared to frequently prescribed endocrine treatments for advanced disease like tamoxifen, anastrozole, letrozole and exemestane, fulvestrant is well tolerated. If biopsied cancer cells can be shown befor
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Contact: David Bricker
brickerd@indiana.edu
812-856-9035
Indiana University
Source:Eurekalert  

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Breast cancer drug fulvestrant appears more effective in the presence of CK8 and CK18
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