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Genetic tests in prediction of effectiveness and toxicity of chemotherapy in cancer patients


Authors: B. Mladosievičová 1;  A. Fotlinová 2;  M. Wawruch 3
Authors place of work: Ústav patologickej fyziológie, Oddelenie klinickej patofyziológie Lekárskej fakulty UK, Bratislava, Slovenská republika prednosta prof. MUDr. Ivan Hulín, DrSc. 1;  Onkologické oddelenie DFNsP, Bratislava, Slovenská republika, prednosta doc. MUDr. Emília Kaiserová, CSc. 2;  Farmakologický ústav Lekárskej fakulty UK, Bratislava, Slovenská republika, prednosta prof. MUDr. Milan Kriška, DrSc. 3
Published in the journal: Vnitř Lék 2005; 51(5): 560-565
Category: Reviews

Summary

In few other fields of clinical practice is the role of pharmacogenetics and pharmacogenomics more important than in anticancer therapy. Genetic alterations in drug metabolism enzyme genes or genes encoding transporters and target proteins can affect not only the toxicity, but also response to commonly used chemotherapy drugs. Gene polymorphisms can influence drug effectiveness and/or toxicity in subgroup of patients treated with 6-mercaptopurine, thioguanine, irinotecan, methotrexate, 5-fluorouracil and platinum chemotherapy. Knowledge regarding single candidate genes polymorphism might be less helpful for predicting potential toxicity and effectiveness of therapy than comprehensive polygenic approach considering combinations of polymorphisms in several genes encoding components in biological or pharmacological pathways. 

Key words:
pharmacogenetics – genetic polymorphism – effectiveness – toxicity – chemotherapy


Zdroje

1. Baker DE. Pharmacogenomics of azathioprine and 6-mercaptopurine in gastroenterologic therapy. Rev Gastroenterol Disord 2003; 3(3): 150–157.

2. Bosma PJ, Chowdhury JR, Bakker C et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyl-transferase 1 in Gilbert’s syndrome. N Engl J Med 1995; 333(18): 1171–1175.

3. Davies SM, Robison LL, Buckley JD et al. Glutathion-S-transferase polymorhisms and outcome of chemotherapy in childhood acute myeloid leukemia. J Clin Oncol 2001; 19: 1279–1287.

4. Dordelmann M, Schrappe M, Reiter A et al. Down’s syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Munster Group. Leukemia 2000; 14(5): 943–944.

5. Evans WE, McLeod HL. Pharmacogenomics – drug disposition, drug targets and side effects. N Engl J Med 2003; 348(6): 538–549.

6. Evans WE. Clinical pharmacology of childhood ALL: Is the same dose optimal for everyone? Med Ped Oncol 1999; 33(3): 191.

7. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999;286(5439): 487–491.

8. Goetz, M. P., Ames, M. M., Weinshilboum, R. M.: Primer on Medical Genomics Part XII. Mayo Clin Proc 2004; 79: 376–384

9. Humerickhouse R, Lohrbach K, Li L et al. Characterization of CPT–11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2. Cancer Res 2000; 60(5): 1189–1192.

10. Chiusolo P, Reddiconto G, Casorelli I et al. Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate. Ann Oncol 2002; 13(12): 1915–1918.

11. Iqbal S, Lenz HJ. Targeted therapy and pharmacogenetic programs. Cancer 2003; 97: 2076–2078.

12. Innocenti I, Iyer L, Ratain MJ. Pharmacogenomics of chemotherapeutic agents in cancer treatment. In: Licinio, J, Ma-Li Wong. Pharmacogenomics. The Search for Individualized Therapies. Weinheim: Wiley-VCH Verlag 2002: 283–303.

13. Jurga Ľ et al. Klinická onkológia a rádioterapia. Bratislava: Slovak Academic Press 2000.

14. Krynetski EY, Evans WE. Pharmacogenetics of cancer therapy: getting personal. Am J Hum Genet 1998; 63(1): 11–16.

15. Krynetski EY, Evans WE. Drug methylation in cancer therapy: lessons from the TPMT polymorphism. Oncogene 2003; 22(47): 7403–7413.

16. Krynetski EY, Evans WE. Genetic polymorphism of thiopurine S-methyltransferase: molecular mechanisms and clinical importance. Pharmacology 2000; 61(3): 136–146.

17. Marshall, E.: Preventing toxicity with a gene test. Science 2003; 302(5645): 588–590.

18. Mihál V, Hajdúch M, Jarošová M. Influence of genetic background on effectiveness/toxicity of current anticancer therapy. Klin Onkol 2000; 13(6): 183–187.

19. Perlík F. Nežádoucí účinky a lékové interakce. Čas Lék Čes 2004; 143: 110–113.

20. Relling MV, Dervieux T. Pharmacogenetics and cancer therapy: Nat Rev Cancer 2001; 1: 99–108.

21. Relling MV, Rubnitz JE, Rivera GK et al. High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet 1999; 354(9172): 34–39.

22. Rivory LP, Bowles MR, Robert J et al. Conversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxy–camptothecin (SN–38), by human liver carboxylesterase. Biochem Pharmacol 1996; 52(7): 1103–1111.

23. Ulrich CM, Robien K, Mc Leod HL. Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nat Rev Cancer 2003; 3(12): 912–920.

24. Valočík G, Rosochová I, Kovács L. Vplyv polymorfizmu ACE génu na funkciu ľavej komory u chorých s diabetom 2. typu. Vnitř Lék 2003; 49(3): 181–184.

25. Zaloudik J. Predictors or statistics versus individual effects of chemotherapy. Vnitř Lék 2002; 48(11): 1001–1003.

26. Zaloudik J. Do we need predictive oncology? Acta Chemotherapeutica 2003; 12(5): 22–23.

27. Villafranca E, Okruzhnov Y, Dominguez MA et al. Polymorphisms of the repeated sequences in the enhancer region of the thymidylat syntase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J Clin Oncol 2001; 19: 1779–1786.

Štítky
Diabetology Endocrinology Internal medicine

Článok vyšiel v časopise

Internal Medicine

Číslo 5

2005 Číslo 5
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