Update on pharmacogenetics in cancer chemotherapy.
This review describes how genetic differences among patients may change the therapeutic outcome in cancer chemotherapy. Severe toxicity in genetically predisposed patients is predominantly associated with mutations in drug metabolism enzyme genes, and an update on genetic intolerance to 6-mercaptopurine, 5-fluorouracil, and irinotecan is provided. Moreover, recent findings pointed out that the methylenetetrahydrofolate reductase (MTHFR) C677T mutation might change patient susceptibility to the toxic effects of the cyclophosphamide, methotrexate, 5-fluorouracil (CMF) regimen and raltitrexed. Finally, it is emerging that not only toxicity, but also response to chemotherapy could be influenced by pharmacogenetic determinants, and the clinical relevance of polymorphisms in thymidylate synthase (TS) and glutathione-S-transferase (GST) genes is discussed.
Innocenti
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Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, Cancer Research Center, The University of Chicago, Chicago, IL, USA.
Ratain
M J
MJ
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics; D013940:Thymidylate Synthase / Q000235:genetics
D000970:Antineoplastic Agents; D013940:Thymidylate Synthase; D005982:Glutathione Transferase