An in vitro model showing adaptation to long-term oestrogen deprivation highlights the clinical potential for targeting kinase pathways in combination with aromatase inhibition

Steroids. 2011 Jul;76(8):772-6. doi: 10.1016/j.steroids.2011.02.035. Epub 2011 Apr 6.

Abstract

Aromatase inhibitors (AI) have improved the treatment of oestrogen receptor positive (ER+) breast cancer. Despite the efficacy of these agents over 40% of patients relapse with endocrine resistant disease. Here we describe an in vitro model of acquired resistance to long-term oestrogen deprivation (LTED). The LTED cells retain expression of the ER and appear hypersensitive to oestrogen as a result of altered kinase activity. Furthermore analysis of temporal changes in gene expression during the acquisition of resistance highlight growth factor receptor pathways as key mediators of this adaptive process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anastrozole
  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis
  • Aromatase Inhibitors / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogens / metabolism*
  • Female
  • Fulvestrant
  • Gene Expression Profiling
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Models, Biological*
  • Nitriles / therapeutic use
  • Postmenopause
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Recurrence
  • Triazoles / therapeutic use

Substances

  • Aromatase Inhibitors
  • Estrogens
  • Nitriles
  • Receptors, Estrogen
  • Triazoles
  • Fulvestrant
  • Anastrozole
  • Estradiol
  • Insulin-Like Growth Factor I