Mechanism-based discovery as an approach to identify the next generation of estrogen receptor modulators Donald P. McDonnell Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA 1 Correspondence: Department of Pharmacology and Cancer Biology, Duke University Medical Center, 6259 LSRC, Box 3813, Durham, NC 27710, USA. E-mail: donald.mcdonnel@duke.edu THE ESTROGEN RECEPTOR (ER) signal transduction pathway is the primary target of the hormonal therapies used for the treatment and prevention of breast cancer. Interestingly, although animal studies performed over a century ago first suggested a link between the ovaries (estrogen production) and growth of breast tumors, definition of the molecular basis for this association and its pharmaceutical exploitation has occurred relatively recently. In the realm of breast cancer chemotherapy, compounds like tamoxifen have emerged which function as antiestrogens by directly blocking the binding of estrogen(s) to their receptors in breast tumors. The aromatase inhibitors, such as letrazole and anastrazole, inhibit estrogen production while high dose progestins attenuate ER signaling by an as yet unknown mechanism. Together, these hormonal therapies have been extremely successful and have improved both mortality and morbidity in this disease. However, as we begin to fully understand the complexities of estrogen
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Mechanism-based discovery as an approach to identify the next generation of estrogen receptor modulators
McDonnell, Donald P.
Follow The FASEB Journal
, Volume 20 (14): 2432
Fed of American Socs for Experimental Biology – Dec 1, 2006
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