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 varia bility in tumor responses and host toxicity. This variation may be caused b y genetic differences in the enzymes involved in the metabolism of anticanc er agents. Anti-cancer agents, such as 6-mercaptopurine, 5-fluorouracil, an d irinotecan, have a narrow therapeutic index that can sometimes result in severe life-threatening toxicities. The impact of polymorphisms in metaboli zing enzymes (thiopurine S-methyltransferase, dihydropyrimidine dehydrogena se, and uridine diphosphate glucuronosyltransferase) that participate signi ficantly in the disposition of these anticancer agents is discussed.