title: Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine.
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.
authors: Experimental & Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors: Elena
authors: E
authors: De Mattia
authors: Experimental & Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors: Erika
authors: E
authors: Cecchin
authors: Experimental & Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors: Rossana
authors: R
authors: Roncato
authors: Experimental & Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy.
authors: Giuseppe
authors: G
authors: Toffoli
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000090702:Constitutive Androstane Receptor; D051536:Hepatocyte Nuclear Factors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D057285:Precision Medicine; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D000090702:Constitutive Androstane Receptor; D051536:Hepatocyte Nuclear Factors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid
keywords: CAR; HNFs; PXR; cancer; chemotherapy; inflammation; metabolic enzymes; pharmacogenetics; polymorphisms; transporters