Selective Estrogen receptor degraders (SERDs) for the treatment of breast cancer: An overview

Eur J Med Chem. 2023 Aug 5:256:115422. doi: 10.1016/j.ejmech.2023.115422. Epub 2023 May 4.

Abstract

Discovery of SERDs has changed the direction of anticancer research, as more than 70% of breast cancer cases are estrogen receptor positive (ER+). Therapies such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI's) have been effective, but due to endocrine resistance, SERDs are now considered essential therapeutics for the treatment of ER+ breast cancer. The present review deliberates the pathophysiology of SERDs from the literature covering various molecules in clinical trials. Estrogen receptors active sites distinguishing characteristics and interactions with currently available FDA-approved drugs have also been discussed. Designing strategy of previously reported SERDs, their SAR analysis, in silico, and the biological efficacy have also been summarized along with appropriate examples.

Keywords: Anti-estrogenic; Aromatase; Breast cancer; ER-α; ER-β; Elacestrant; Estrogen; Fulvestrant; Orserdu; SERM; Selective estrogen receptor degraders (SERDs).

Publication types

  • Review

MeSH terms

  • Aromatase Inhibitors / pharmacology
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Estrogen Antagonists / therapeutic use
  • Estrogen Receptor alpha
  • Female
  • Humans
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators / chemistry
  • Selective Estrogen Receptor Modulators / pharmacology
  • Selective Estrogen Receptor Modulators / therapeutic use

Substances

  • Receptors, Estrogen
  • Estrogen Antagonists
  • Selective Estrogen Receptor Modulators
  • Aromatase Inhibitors
  • Estrogen Receptor alpha