The aryl hydrocarbon receptor (AhR) as a breast cancer drug target

Med Res Rev. 2020 May;40(3):972-1001. doi: 10.1002/med.21645. Epub 2019 Nov 12.

Abstract

Breast cancer is the most common cancer in women, with more than 1.7 million diagnoses worldwide per annum. Metastatic breast cancer remains incurable, and the presence of triple-negative phenotypes makes targeted treatment impossible. The aryl hydrocarbon receptor (AhR), most commonly associated with the metabolism of xenobiotic ligands, has emerged as a promising biological target for the treatment of this deadly disease. Ligands for the AhR can be classed as exogenous or endogenous and may have agonistic or antagonistic activity. It has been well reported that agonistic ligands may have potent and selective growth inhibition activity in a number of oncogenic cell lines, and one (aminoflavone) has progressed to phase I clinical trials for breast cancer sufferers. In this study, we examine the current state of the literature in this area and elucidate the promising advances that are being made in hijacking the cytosolic-to-nuclear pathway of the AhR for the possible future treatment of breast cancer.

Keywords: aryl hydrocarbon receptor; breast cancer; cancer drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Basic Helix-Loop-Helix Transcription Factors / chemistry*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Female
  • Flavonoids / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Ligands
  • Molecular Conformation
  • Oncogenes
  • Pharmaceutical Preparations
  • Protein Domains
  • Receptors, Aryl Hydrocarbon / chemistry*

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Flavonoids
  • Ligands
  • Pharmaceutical Preparations
  • Receptors, Aryl Hydrocarbon
  • aminoflavone