The advent of endocrine therapy has led to significant advances in the treatment of cancer. In particular, modulation of the estrogen receptor and the proteins that regulate estrogen synthesis have led to improved treatments for breast cancer. The clinical manifestation of tissue-selective compounds such as tamoxifen has led to the identification of SERMs as viable treatments for therapies ranging from breast cancer to osteoporosis. Moreover, this discovery has laid the groundwork for the identification of tissue-selective agents for other steroid receptors such as the androgen, glucocorticoid, and progesterone receptors, i.e., SARMs, SGRMs, and SPRMs, respectively. Future research will lie in obtaining the appropriate tissue selectivity for the disease state in question. An in depth understanding of ligand-protein interactions, including co-regulators, will be important for fine-tuning tissue-selective pharmacology. In the area of the regulation of estrogen synthesis, small-molecule, orally active GnRH antagonists have been investigated and are being clinically validated for the treatment of gynecological disorders and prostate cancer. Combination studies of inhibitors of hormone action with inhibitors of hormone synthesis are underway and may provide benefits in clinical outcomes.
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