Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dose adjustment of drug administration for each patient has been performed based on counts of some factors such as body surface area, age of the patient, performance status, renal and/or liver function. Pharmacokinetic and pharmacodynamic analyses have been investigated by measuring the plasma concentration of a drug and observing the drug effects. However, prior to drug administration it is difficult to predict unexpected, severe drug toxicity, which depends on the individual differences among patients. Recent progress in human genome analysis has been providing tools for new approaches to disease treatment based on individual differences using genetic information. This review focuses on the drug metabolizing enzyme and its genetic polymorphisms in cancer chemotherapy. We describe the recent findings on pharmacogenomics between toxicity and the genetic polymorphisms of the thiopurine methyltransferase (TPMT) gene, dihydropyrimidine dehydrogenase (DPYD) gene, methylenetetrahydrofolate reductase (MTHFR) gene, and uridine diphosphate glucuronosyltransferase (UGT1A1 and UGT1A7) gene. We need to accumulate clinical data based on the variation of genetic profiling as well as pharmacogenetic information. Such data will help tailor cancer chemotherapy to an individual's predisposition in the near future.
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PMID:[Pharmacogenomic approaches for prevention of drug toxicity in cancer chemotherapy]. 1266 88

Conventionally adjustments of the dose of chemotherapeutic treatment could be uneffective in preventing toxicity and response variability. New strategies for individualization of treatment in cancer patients are becoming an emerging issue in the clinical practice. Pharmacogenetics is undoubtedly an important source of information in this respect deepening the complex correlation existing between individual genetic profile and the response to therapy in terms of toxicity and activity. Several polymorphisms, i.e. genetic mutations with a frequency > 1% in a given population, have been described for genes encoding proteins involved in the metabolism of the drugs employed in the treatment of gastric cancer. TS (thymidilate synthase) and DPD (dihydropyrimidine dehydrogenase) polymorphisms are implicated in the development of toxicity and in the efficacy of 5-fluorouracil (5FU). XRCC1 (X-ray cross-complementing group 1), ERCC1 (excision cross-complementing gene) and GSTP1 (glutathione S-transferase) have a role in the development of pharmacoresistance to platinum derivatives. MTHFR (5, 10 methylenetetrahydrofolate reductase) C677T polymorphism is important in methotrexate (MTX) metabolism. UGT1A1 (uridine diphoshate-glucuronosyltransferase 1A1) is involved on irinotecan metabolism. MRP2 (multi-drug resistance associated protein) and MDR1 (multi-drug resistance gene) are involved in irinotecan as well as anthracyclines transport. In conclusion, the clinical applications of pharmacogenetics could represent a new insight to accurately determine the proper drug and dose to be used in each individual patient.
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PMID:Pharmacogenetics of stomach cancer. 1291 84