title: Pharmacogenetics of irinotecan, doxorubicin and docetaxel transporters in Asian and Caucasian cancer patients: a comparative review.
abstract: Drug efflux and influx transporters play critical roles in regulating the cellular drug disposition and modulating the pharmacokinetics and pharmacodynamics of anti-cancer agents, which may potentially alter treatment outcomes. The efficiency of drug transport is often dependent on the expression and activity of these membrane-bound proteins, factors which have been shown to be regulated by genes that are known to be highly polymorphic in different ethnic populations. The role of drug transporters becomes even more critical for anti-cancer agents due to the narrow therapeutic windows that separate treatment response and toxicities for these agents. Moreover, high inter-individual variability in the disposition of anti-cancer agents often results in variable treatment outcomes among patients receiving standard doses of the same drug. Such variability has been attributed at least in part to polymorphisms in genes encoding drug-metabolizing enzymes and transporter. To date, numerous pharmacogenetic studies have investigated the associations between variants in the ABC and SLC transporters genes with drug disposition, treatment outcomes and drug-induced toxicities. However, the strengths of these associations and their clinical relevance in different ethnic populations have not been critically examined. This review aims to summarize and evaluate the implications of pharmacogenetic variants in the ABC and SLC transporters genes on the pharmacokinetics and clinical outcomes of three anti-cancer agents: irinotecan, docetaxel and doxorubicin in Caucasian and Asian patients.
authors.affiliation: a Clinical Pharmacology Laboratory, Division of Medical Sciences , Humphrey Oei Institute of Cancer Research , National Cancer Center Singapore , Singapore.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Chen
authors.affiliation: b Clinical Pharmacology, SingHealth , Singapore.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sutiman
authors.affiliation: b Clinical Pharmacology, SingHealth , Singapore.
authors.forename: Clara Zhenxian
authors.initials: CZ
authors.lastname: Zhang
authors.affiliation: a Clinical Pharmacology Laboratory, Division of Medical Sciences , Humphrey Oei Institute of Cancer Research , National Cancer Center Singapore , Singapore.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: a Clinical Pharmacology Laboratory, Division of Medical Sciences , Humphrey Oei Institute of Cancer Research , National Cancer Center Singapore , Singapore.
authors.forename: Shirley
authors.initials: S
authors.lastname: Lam
authors.affiliation: c Singapore Eye Research Institute , Singapore.|d Department of Ophthalmology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore.|e Division of Human Genetics , Genome Institute of Singapore , Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: a Clinical Pharmacology Laboratory, Division of Medical Sciences , Humphrey Oei Institute of Cancer Research , National Cancer Center Singapore , Singapore.|b Clinical Pharmacology, SingHealth , Singapore.|f Office of Clinical Sciences , Duke-NUS Graduate Medical School , Singapore.
authors.forename: Balram
authors.initials: B
authors.lastname: Chowbay
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077143:Docetaxel; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics; D000070590:Solute Carrier Proteins / Q000235:genetics; D043823:Taxoids / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome; D044465:White People / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D000070590:Solute Carrier Proteins; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D004317:Doxorubicin; D002166:Camptothecin
keywords: ABC; Drug transporters; SLC; docetaxel; doxorubicin; irinotecan