Oral Selective Estrogen Receptor Downregulators (SERDs), a Breakthrough Endocrine Therapy for Breast Cancer

J Med Chem. 2015 Jun 25;58(12):4883-7. doi: 10.1021/acs.jmedchem.5b00760. Epub 2015 Jun 3.


Drugs that inhibit estrogen receptor alpha (ERα) or that block the production of estrogens remain frontline interventions in the treatment and management of breast cancer at all stages. However, resistance to endocrine therapies, especially in the setting of advanced disease, remains an impediment to durable clinical responses. Although the mechanisms underlying resistance to existing agents are complex, preclinical studies suggest that selective estrogen receptor downregulators (SERDs), molecules which eliminate ERα expression, may have particular utility in the treatment of breast cancers that have progressed on tamoxifen and/or aromatase inhibitors. The discovery and development of orally bioavailable SERDs provide the opportunity to evaluate the utility of eliminating ERα expression in advanced metastatic breast cancers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / chemistry*
  • Antineoplastic Agents, Hormonal / pharmacology
  • Aromatase Inhibitors / chemistry
  • Aromatase Inhibitors / pharmacology
  • Breast / drug effects
  • Breast / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Drug Discovery*
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Humans
  • Selective Estrogen Receptor Modulators / chemistry*
  • Selective Estrogen Receptor Modulators / pharmacology
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology


  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Estrogen Receptor alpha
  • Selective Estrogen Receptor Modulators
  • Tamoxifen