title: Pharmacogenetics of the nuclear hormone receptors: the missing link between environment and drug effects?
abstract: In the last decade, genetic variations in ABC/SLC transporters and phase I/II enzymes have raised pharmacogenetic markers as being predictive to the attention of researchers in the field of personalized medicine in oncology. However, it is becoming evident that the sequence variations in these genes cannot address by themselves the sharp interindividual variability in drug effects. Recently, nuclear receptors (NRs), including pregnane X receptor, constitutive androstane receptor, retinoid X receptor, farnesoid X receptor, liver X receptor, vitamin D receptor, peroxisome proliferator-activated receptors and HNF4A, have demonstrated key roles in regulating transporter and metabolic gene expression in response to xeno/endobiotics, as well as antineoplastic drugs. These findings attracted interest to the genetics of the NRs for their possible role in influencing the metabolism and pharmacological profiles of chemotherapeutics. In this review, we aim to summarize the most recent findings in the innovative field of NR pharmacogenetics and findings in how they could integrate with more traditional markers in order to improve drug treatment personalization.
authors.affiliation: Experimental & Clinical Pharmacology Unit, Centro di Riferimento Oncologico-National Cancer Institute, Via Franco Gallini, 2, 33081, Aviano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Mattia
authors.forename: Eva
authors.initials: E
authors.lastname: Dreussi
authors.forename: Erika
authors.initials: E
authors.lastname: Cecchin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D059647:Gene-Environment Interaction; D006801:Humans; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D010597:Pharmacogenetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D015262:Xenobiotics / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D015262:Xenobiotics