Skip to main content
Journal cover image

The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer.

Publication ,  Journal Article
McDonnell, DP; Wardell, SE
Published in: Curr Opin Pharmacol
December 2010

Our understanding of the molecular mechanisms underlying the pharmacological actions of estrogen receptor (ER) ligands has evolved considerably in recent years. Much of this knowledge has come from a detailed dissection of the mechanism(s) of action of the Selective Estrogen Receptor Modulators (SERMs) tamoxifen and raloxifene, so called for their ability to function as ER agonists or antagonists depending on the tissue in which they operate. These mechanistic insights have had a significant impact on the discovery of second generation SERMs, some of which are in late stage clinical development for the treatment/prevention of breast cancer as well as other estrogenopathies. In addition to the SERMs, however, have emerged the Selective Estrogen Degraders (SERDs), which as their name suggests, interact with and facilitate ER turnover in cells. One drug of this class, fulvestrant, has been approved as a third line treatment for ER-positive metastatic breast cancer. Whereas the first generation SERMs/SERDs were discovered in a serendipitous manner, this review will highlight how our understanding of the molecular pharmacology of ER ligands has been utilized in the development of the next generation of SERMs/SERDs, some of which are likely to have a major impact on the pharmacotherapy of breast cancer.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Curr Opin Pharmacol

DOI

EISSN

1471-4973

Publication Date

December 2010

Volume

10

Issue

6

Start / End Page

620 / 628

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Signal Transduction
  • Selective Estrogen Receptor Modulators
  • Receptors, Estrogen
  • Pharmacology & Pharmacy
  • Nuclear Receptor Coactivators
  • Molecular Targeted Therapy
  • Molecular Conformation
  • Ligands
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McDonnell, D. P., & Wardell, S. E. (2010). The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer. Curr Opin Pharmacol, 10(6), 620–628. https://doi.org/10.1016/j.coph.2010.09.007
McDonnell, Donald P., and Suzanne E. Wardell. “The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer.Curr Opin Pharmacol 10, no. 6 (December 2010): 620–28. https://doi.org/10.1016/j.coph.2010.09.007.
McDonnell, Donald P., and Suzanne E. Wardell. “The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer.Curr Opin Pharmacol, vol. 10, no. 6, Dec. 2010, pp. 620–28. Pubmed, doi:10.1016/j.coph.2010.09.007.
Journal cover image

Published In

Curr Opin Pharmacol

DOI

EISSN

1471-4973

Publication Date

December 2010

Volume

10

Issue

6

Start / End Page

620 / 628

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Signal Transduction
  • Selective Estrogen Receptor Modulators
  • Receptors, Estrogen
  • Pharmacology & Pharmacy
  • Nuclear Receptor Coactivators
  • Molecular Targeted Therapy
  • Molecular Conformation
  • Ligands
  • Humans