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  • Title: Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment.
    Author: Patel HK, Bihani T.
    Journal: Pharmacol Ther; 2018 Jun; 186():1-24. PubMed ID: 29289555.
    Abstract:
    Breast cancer is the most frequently diagnosed cancer in women, with estrogen receptor positive (ER+) breast cancer making up approximately 75% of all breast cancers diagnosed. Given the dependence on active ER signaling in these tumors, the predominant treatment strategy has been to inhibit various aspects of this pathway including directly antagonizing ER with the use of selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs). Interestingly, the dependence on ER for breast cancer growth is often retained even after progression through several lines of antiestrogen therapy, making ER a bonafide biomarker for this cancer subtype and driving the continued research and development of novel ER-targeted therapeutics to treat this patient population. This, combined with the continuous discovery of mechanisms underlying endocrine resistance, is resulting in a continually evolving treatment landscape for ER+ breast cancer. This review discusses various ER antagonists investigated for the treatment of breast cancer, outlining their pharmacological and tissue-specific mechanisms of action as well as their specified use within the ER+ breast cancer setting. In addition, mechanisms of resistance to SERMs and SERDs, the use of ER antagonists in combination therapy strategies, and the ongoing development of novel drugs are also reviewed in the context of the changing clinical landscape of ER+ breast cancer. Lastly, the role of SERMs and SERDs in non-breast cancer indications is also discussed.
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