Pharmacogenetics of stomach cancer.
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.
Toffoli
Giuseppe
G
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Via Pedemontana Occidentale 12, Aviano, PN.
Cecchin
Erika
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D004268:DNA-Binding Proteins / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases; D014453:Glucuronosyltransferase / Q000378:metabolism; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D026901:Membrane Transport Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011506:Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D000076105:X-ray Repair Cross Complementing Protein 1
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004720:Endonucleases; D014453:Glucuronosyltransferase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D026901:Membrane Transport Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011506:Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000715087:ABCC2 protein, human; C000619371:XRCC1 protein, human; C496556:GSTP1 protein, human; C071447:ERCC1 protein, human