Pharmacogenetics of Drug Metabolizing Enzymes and Transporters: Effects on Pharmacokinetics and Pharmacodynamics of Anticancer Agents

Norman      H. Lee

doi:10.2174/187152010794474019

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.

Keywords: Pharmacogenetics, single nucleotide polymorphisms, genetic variation, thiopurine S-methyltransferase, thymidylate synthase, dihydropyrimidine dehydrogenase, ATP-binding cassette transporters, multidrug resistance-associated protein, cancer health disparities.