title: Pharmacogenetics of drug metabolizing enzymes and transporters: effects on pharmacokinetics and pharmacodynamics of anticancer agents.
abstract: There is wide interpatient variability in drug response and toxicity to standard doses of most anticancer medications. Genetic polymorphisms in genes encoding metabolic enzymes, receptors and drug transporters targeted by anticancer medications are often found, in part, to be responsible for the observed variability. Approximately 80% of all sequence variations residing in genes is in the form of single nucleotide polymorphisms or SNPs. The location of SNPs can be in the protein coding sequence, regulatory regions or at exon-intron boundaries of genes. Adverse drug reactions resulting from these sequence variations are due to changes in the activity of the encoded protein (in many instances the protein is non-functional) or perturbations in the level of gene expression. The goal of pharmacogenetic testing is to identify genetic polymorphisms that predispose patients to an adverse drug reaction, thereby allowing the health care provider to make informed decisions pertaining to the type of drug, dosage and dosage scheduling to be administered.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University Medical Center, Washington, DC 20037, USA. phmnhl@gwumc.edu
authors.forename: Norman H
authors.initials: NH
authors.lastname: Lee
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019450:Genes, MDR; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D013940:Thymidylate Synthase / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D042943:Dihydrouracil Dehydrogenase (NADP); D008780:Methyltransferases; D013940:Thymidylate Synthase; C022745:thiopurine methyltransferase