The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5-fluorouracil.
There is increasing evidence supporting the important role of genetics in determining the effect (response and toxicity) to cancer chemotherapy. This has included both pharmacogenetics, where the alteration of a gene coding for an important drug metabolizing enzyme results in increased toxicity (and occasionally altered efficacy), and pharmacogenomics, where knowledge of the expression of genes critical to the action of the cancer chemotherapy drug can be used to individualize therapy. This manuscript focuses on the widely used cancer chemotherapy drug 5-fluorouracil (5-FU) to illustrate the following 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 potential value of pharmacogenomics in designing new drugs.
Diasio
R B
RB
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, UAB Comprehensive Cancer Center, University of Alabama at Birmingham, AL 35294, USA. robert.diasio@ccc.uab.edu
Johnson
M R
MR
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010597:Pharmacogenetics
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil