Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies

Future Med Chem. 2015 Aug;7(12):1511-9. doi: 10.4155/fmc.15.93. Epub 2015 Aug 26.

Abstract

Endocrine therapy has become one of most effective forms of targeted adjuvant therapy for hormone-sensitive breast cancer and may be given after surgery or radiotherapy, and also prior, or subsequent to chemotherapy. Current commonly used drugs for adjuvant endocrine therapy can be divided into following three classes: selective estrogen receptor modulators, aromatase inhibitors and selective estrogen receptor downregulators. Tumor cells can develop resistance to endocrine therapy, a major obstacle limiting the success of breast cancer treatment. The complicated crosstalk, both genomic and nongenomic, between estrogen receptors and growth factors was considered to be a crucial factor contributing to endocrine resistance. However, resistance to this therapy is thought to be a progressive, step-wise process, and the underlying mechanism remains unclear. In this review, we summarize the possible biological and molecular mechanisms that underlie endocrine resistance, and discuss some novel strategies to overcoming these issues.

Keywords: breast cancer; drug resistance; endrocrine therapeutics; estrogen receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aromatase Inhibitors / pharmacology*
  • Aromatase Inhibitors / therapeutic use
  • Breast / drug effects*
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Molecular Targeted Therapy / methods
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Aromatase Inhibitors
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • Receptor, ErbB-2
  • TOR Serine-Threonine Kinases