Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine

Research output: Contribution to journalReview article

Abstract

Great research effort has been focused on elucidating the contribution of host genetic variability on pharmacological outcomes in cancer. Nuclear receptors have emerged as mediators between environmental stimuli and drug pharmacokinetics and pharmacodynamics. The pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors have been reported to regulate transcription of genes that encode drug metabolizing enzymes and transporters. Altered nuclear receptor expression has been shown to affect the metabolism and pharmacological profile of traditional chemotherapeutics and targeted agents. Accordingly, polymorphic variants in these genes have been studied as pharmacogenetic markers of outcome variability. This review summarizes the state of knowledge about the roles played by pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factor expression and genetics as predictive markers of anticancer drug toxicity and efficacy, which can improve cancer precision medicine.

Original languageEnglish
Pages (from-to)1547-1571
Number of pages25
JournalPharmacogenomics
Volume17
Issue number14
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • cancer
  • CAR
  • chemotherapy
  • HNFs
  • inflammation
  • metabolic enzymes
  • pharmacogenetics
  • polymorphisms
  • PXR
  • transporters

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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