The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5-fluorouracil

There is increasing evidence supporting the important role of genetics in d etermining the effect (response and toxicity) to cancer chemotherapy, This has included both pharmacogenetics, where the alteration of a gene coding f or an important drug metabolizing enzyme results in increased toxicity land occasionally altered efficacy), and pharmacogenomics, where knowledge of t he expression of genes critical to the action of the cancer chemotherapy dr ug can be used to individualize therapy. This manuscript focuses on the wid ely used cancer chemotherapy drug 5-fluorouracil (5-FU) to illustrate the f ollowing concepts: (1) The effect of the pharmacogenetic syndrome known as dihydropyrimidine dehydrogenase (DPD) deficiency on 5-FU pharmacology; (2) the role of pharmacogenomics in individualizing 5-FU therapy, and (3) the p otential value of pharmacogenomics in designing new drugs. Copyright (C) 20 00 S. KargerAG, Basel.