title: Nuclear receptors and drug metabolism for the personalization of cancer therapy.
abstract: BACKGROUND
  A remarkable inter-individual variability in the occurrence of severe side effects represents an ongoing challenge in cancer treatment. Significant research efforts have focused on elucidating the contribution of the host genetic variability, but only a few markers have been identified for use in clinical practice. Several studies demonstrated that PXR and CAR activation can affect the expression of genes involved in absorption, distribution, metabolism and excretion (ADME) of antineoplastic drugs. The study of the host genetic background of Pregnane X Receptor (PXR; NR1I2) and Constitutive Androstane Receptor (CAR; NR1I3 and NR1I4), represents a new and attractive strategy to discern variability in ADME of antineoplastic drugs.
  
  
  METHODS
  An update of the most important findings about investigational CAR and PXR pharmacogenetic markers of anti-cancer drugs toxicity is provided.
  
  
  CONCLUSIONS
  A differential activation of PXR and CAR can affect the pharmacokinetics and pharmacodynamics of antineoplastic drugs. Pharmacogenetics studies published up to date provide encouraging even if exploratory results. Future large and prospective studies will clarify the clinical value of PXR and CAR genetic markers in treatment personalization.
authors.affiliation: a Experimental and Clinical Pharmacology , Centro di Riferimento Oncologico- National Cancer Institute , Aviano , Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Cecchin
authors.affiliation: a Experimental and Clinical Pharmacology , Centro di Riferimento Oncologico- National Cancer Institute , Aviano , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Mattia
authors.affiliation: a Experimental and Clinical Pharmacology , Centro di Riferimento Oncologico- National Cancer Institute , Aviano , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000090702:Constitutive Androstane Receptor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010597:Pharmacogenetics; D057285:Precision Medicine; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000090702:Constitutive Androstane Receptor; C000625852:NR1I2 protein, human; C000716327:NR1I3 protein, human; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid
keywords: CAR; Cancer; PXR; nuclear receptors; toxicity