SELECTiVE ESTROGEN RECEPTOR MODULATORS

Abstract

The sex hormone estrogen is important for many physiological processes. Prolonged. stimulation of breast ductal epithelium by estrogen, however, can contribute to the development and progression of breast cancer, and treatments designed to block estrogen's effects are important options in the clinic.

Tamoxifen and other similar drugs are effective in breast cancer prevention and treatment by inhibiting the proliferative effects of estrogen that are mediated through the estrogen receptor (ER).

However. these drugs also have many estrogenic effects depending on the tissue and gene, and they are more appropriately called selective estrogen receptor modulators (SERMs). SERMs bind ER alter receptor conformation, and facilitate binding of coregulatory proteins that activate or repress transcriptional activation of estrogen target genes. Theoretically, SERMs could be synthesized that could exhibit nearly complete agonist activity on one hand or pure anti-estrogenic activity on the other depending on their functional activities, SERMs could then be developed for a variety of clinical uses, including prevention and treatment of osteoporosis, treatment and prevention of estrogen regulated malignancies, and even for hormone replacement therapy.