Inherited variations in drug-metabolizing enzymes: significance in clinical oncology.
Pharmacogenetics has emerged as a novel and challenging area of interest in oncology. Cancer chemotherapy is characterized by major intersubject variability in tumor responses and host toxicity. This variation may be caused by genetic differences in the enzymes involved in the metabolism of anticancer agents. Anticancer agents, such as 6-mercaptopurine, 5-fluorouracil, and irinotecan, have a narrow therapeutic index that can sometimes result in severe life-threatening toxicities. The impact of polymorphisms in metabolizing enzymes (thiopurine S-methyltransferase, dihydropyrimidine dehydrogenase, and uridine diphosphate glucuronosyltransferase) that participate significantly in the disposition of these anticancer agents is discussed.
Iyer
L
L
Department of Medicine and Committee on Clinical Pharmacology, The University of Chicago, Chicago, Illinois 60637, USA. liyer@mcis.bsd.uchicago.edu
D000483:Alleles; D000970:Antineoplastic Agents / Q000378:metabolism*; D042943:Dihydrouracil Dehydrogenase (NADP); D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic
D000970:Antineoplastic Agents; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D008780:Methyltransferases; C022745:thiopurine methyltransferase; D014453:Glucuronosyltransferase