Estrogen receptors as targets for drug development for breast cancer, osteoporosis and cardiovascular diseases

Thresia Thomas, Michael A. Gallo, T. J. Thomas

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations

Abstract

Estrogen receptors (ERs) are proteins that mediate the action of estradiol and a series of natural and synthetic chemicals that mimic the estradiol structure. Estrogenic action was initially attributed to a single type of ER, now known as ERα, but ERβ was discovered in 1995. Tissue specific distribution and the intensity of expression of these proteins determine the first response of tissues to estrogenic compounds. Estrogens and ERs play a major role in the origin and progression of breast cancer, and antiestrogens that block ER function are useful for breast cancer prevention and treatment. Estrogen mimetics, however, do not fall into distinct categories of agonists and antagonists, since their action is regulated by tissue-specific expression of a number of auxiliary proteins called coactivators or corepressors. In addition, small molecules such as polyamines, fattyacids, and thioredoxin may modulate ER function. Estrogenic functions encompass multiple organ systems, including the reproductive, skeletal, cardiovascular, and nervous system. Estrogens are critical for bone remodeling and mineralization so that estrogen replacement therapy is proven to strengthen bone health in post-menopausal women. Ideally, selective blockade of ER function in breast epithelial cells should be accompanied by growth support on bone and cardiovascular systems. The details of estrogenic function in different organs are to be fully realized, in order to better utilize selective estrogen receptor modulators (SERMs) to fight not only breast cancer but also osteoporosis and cardiovascular diseases. Current research on SERMs points toward accomplishing this goal by exploiting ER as a versatile target against multiple diseases.

Original languageEnglish (US)
Pages (from-to)483-499
Number of pages17
JournalCurrent Cancer Drug Targets
Volume4
Issue number6
DOIs
StatePublished - Sep 2004

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

Keywords

  • Breast cancer
  • Cardiovascular diseases
  • Estrogen receptor
  • Estrogens
  • Hormone replacement therapy
  • Osteoporosis
  • Selective estrogen receptor modulator (SERM)

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