title: Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity.
abstract: Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.
authors.affiliation: Pharmacotherapeutics Unit, Department of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Rafid Salim
authors.initials: RS
authors.lastname: Jabir
authors.forename: Rakesh
authors.initials: R
authors.lastname: Naidu
authors.forename: Muhammad Azrif Bin Ahmad
authors.initials: MA
authors.lastname: Annuar
authors.forename: Gwo Fuang
authors.initials: GF
authors.lastname: Ho
authors.forename: Murali
authors.initials: M
authors.lastname: Munisamy
authors.forename: Johnson
authors.initials: J
authors.lastname: Stanslas
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D000077143:Docetaxel; D005260:Female; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D017239:Paclitaxel / Q000627:therapeutic use; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D043823:Taxoids / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity
chemical_list: C000715087:ABCC2 protein, human; D000089762:Multidrug Resistance-Associated Protein 2; D029362:Organic Anion Transporters, Sodium-Independent; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel