Pharmacogenetics in cancer treatment.
Interindividual variability in the efficacy and toxicity of drug therapy is associated with polymorphisms in genes encoding drug-metabolizing enzymes, transporters, or drug targets. Pharmacogenetics aims to identify individuals predisposed to high risk of toxicity from conventional doses of cancer chemotherapeutic agents. We review the role of genetic polymorphisms in UGT1A1 and TPMT, as well as mutations in DPD, in influencing drug disposition and toxicity. Recent studies show that pharmacogenetic determinants may also influence treatment outcomes. We discuss the clinical significance of polymorphisms in TS, MTHFR, and FCGR3A, as well as the polymorphic DNA repair genes XPD and XRCC1, in influencing response to chemotherapy and survival outcomes. Finally, the potential implications of transporter pharmacogenetics in influencing drug bioavailability are addressed.
Nagasubramanian
R
R
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA. rnagasub@peds.bsd.uchicago.edu
Innocenti
F
F
Ratain
M J
MJ
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001711:Biotransformation / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D016896:Treatment Outcome
D000970:Antineoplastic Agents