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Pharmacogenomics of Drug-Metabolizing Enzymes and Drug Transporters in Chemotherapy

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Pharmacogenomics in Drug Discovery and Development

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 448))

Summary

There is wide variability in the response of individuals to standard doses of drug therapy. This is an important problem in clinical practice, where it can lead to therapeutic failures or adverse drug events. Polymorphisms in genes coding for metabolizing enzymes and drug transporters can affect drug efficacy and toxicity. Pharmacogenomics aims to identify individuals predisposed to high risk of toxicity and low response from standard doses of anticancer drugs. This chapter focuses on the clinical significance of polymorphisms in drug-metabolizing enzymes and drug transporters in influencing efficacy and toxicity of anticancer therapy. The most important examples to demonstrate the influence of pharmacogenomics on anticancer therapy are thiopurine methyltransferase (TPMT), UGT (uridine diphosphate glucuronosyltransferase) 1A1*28, and DPD (dihydropyrimidine dehydrogenase) *2A, respectively, for 6-mercaptopurine, irinotecan, and 5-fluorouracil therapy. However, in most other anticancer therapies no clear association has been found for polymorphisms in drug-metabolizing enzymes and drug transporters and pharma-cokinetics or pharmacodynamics of anticancer drugs. Evaluation of different regimens and tumor types showed that polymorphisms can have different, sometimes even contradictory, pharmacokinetic and pharmacodynamic effects in different tumors in response to different drugs. The clinical application of pharmacogenomics in cancer treatment therefore requires more detailed information regarding the different polymorphisms in drug-metabolizing enzymes and drug transporters. A greater understanding of complexities in pharmacogenomics is needed before individualized therapy can be applied on a routine basis.

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References

  1. Dorne, J.L. (2004) Impact of inter-individual differences in drug metabolism and pharmacoki-netics on safety evaluation. Fundam. Clin. Pharmacol. 18, 609–620.

    Article  CAS  PubMed  Google Scholar 

  2. Erichsen, H.C., and Chanock, S.J. (2004) SNPs in cancer research and treatment. Br. J. Cancer. 90, 747–751.

    Article  CAS  PubMed  Google Scholar 

  3. van den Bongard, H.J., Mathot, R.A., Beijnen, J.H., et al. (2000) Pharmacokinetically guided administration of chemotherapeutic agents. Clin. Pharmacokinet. 39, 345–367.

    Article  PubMed  Google Scholar 

  4. de Jonge, M.E., Huitema, A.D., Schellens, J.H., et al. (2005) Individualised cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation: a review. Clin. Pharmacokinet. 44, 147–173.

    Article  PubMed  Google Scholar 

  5. Bosch, T.M., Meijerman, I., Beijnen, J.H., et al. (2006) Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer. Clin. Pharmacokinet. 45, 253–285.

    Article  CAS  PubMed  Google Scholar 

  6. Dehal, S.S., and Kupfer, D. (1997) CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res. 57, 3402–3406.

    CAS  PubMed  Google Scholar 

  7. Jin, Y., Desta, Z., Stearns, V., et al. (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J. Natl. Cancer Inst. 97, 30–39.

    Article  CAS  PubMed  Google Scholar 

  8. Relling, M.V., Evans, W.E., Fonne-Pfister, R., et al. (1989) Anticancer drugs as inhibitors of two polymorphic cytochrome P450 enzymes, debrisoquin and mephenytoin hydroxylase, in human liver microsomes. Cancer Res. 49, 68–71.

    CAS  PubMed  Google Scholar 

  9. Lamba, J.K., Lin, Y.S., Schuetz, E.G., et al. (2002) Genetic contribution to variable human CYP3A-mediated metabolism. Adv. Drug Deliv. Rev. 54, 1271–1294.

    Article  CAS  PubMed  Google Scholar 

  10. Bosch, T.M., Deenen, M., Pruntel, R., et al. (2006) Screening for polymorphisms in the PXR gene in a Dutch population. Eur. J. Clin. Pharmacol. 62, 395–399.

    Article  CAS  PubMed  Google Scholar 

  11. Hustert, E., Zibat, A., Presecan-Siedel, E., et al. (2001) Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab. Dispos. 29, 1454–1459.

    CAS  PubMed  Google Scholar 

  12. Koyano, S., Kurose, K., Saito, Y., et al. (2004) Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab. Dispos. 32, 149–154.

    Article  CAS  PubMed  Google Scholar 

  13. Diasio, R.B., Beavers, T.L., and Carpenter, J.T. (1988) Familial deficiency of dihydropyrimi-dine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J. Clin. Invest. 81, 47–51.

    Article  CAS  PubMed  Google Scholar 

  14. Takimoto, C.H., Lu, Z.H., Zhang, R., et al. (1996) Severe neurotoxicity following 5-fluorour-acil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Clin. Cancer Res. 2, 477–481.

    CAS  PubMed  Google Scholar 

  15. Harris, B.E., Song, R., Soong, S.J., et al. (1990) Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion. Cancer Res. 50, 197–201.

    CAS  PubMed  Google Scholar 

  16. Fleming, R.A., Milano, G., Thyss, A., et al. (1992) Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients. Cancer Res. 52, 2899–2902.

    CAS  PubMed  Google Scholar 

  17. Wei, X., McLeod, H.L., McMurrough, J., et al. (1996) Molecular basis of the human dihydro-pyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J. Clin. Invest. 98, 610–615.

    Article  CAS  PubMed  Google Scholar 

  18. Raida, M., Schwabe, W., Hausler, P., et al. (2001) Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5′-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)-related toxicity compared with controls. Clin. Cancer Res. 7, 2832–2839.

    CAS  PubMed  Google Scholar 

  19. Maring, J.G., van Kuilenburg, A.B., Haasjes, J., et al. (2002) Reduced 5-FU clearance in a patient with low DPD activity to heterozygosity for a mutant allele of the DPYD gene. Br. J. Cancer. 86, 1028–1033.

    Article  CAS  PubMed  Google Scholar 

  20. van Kuilenburg, A.B., Muller, E.W., Haasjes, J., et al. (2001) Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5-fluorouracil: frequency of the common IVS14+1G>A mutation causing DPD deficiency. Clin. Cancer Res. 7, 1149–1153.

    PubMed  Google Scholar 

  21. van Kuilenburg, A.B., Meinsma, R., Zoetekouw, L., et al. (2002) High prevalence of the IVS14 + 1G>A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity. Pharmacogenetics. 12, 555–558.

    Article  PubMed  Google Scholar 

  22. van Kuilenburg, A.B., Meinsma, R., Zoetekouw, L., et al. (2002) Increased risk of grade IV neutropenia after administration of 5-fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: high prevalence of the IVS14+1g>a mutation. Int. J. Cancer. 101, 253–258.

    Article  PubMed  Google Scholar 

  23. Collie-Duguid, E.S., Etienne, M.C., Milano, G., et al. (2000) Known variant DPYD alleles do not explain DPD deficiency in cancer patients. Pharmacogenetics. 10, 217–223.

    Article  CAS  PubMed  Google Scholar 

  24. van Kuilenburg, A.B., Haasjes, J., Richel, D.J., et al. (2000) Clinical implications of dihydro-pyrimidine dehydrogenase (DPD) deficiency in patients with severe 5-fluorouracil-associated toxicity: identification of new mutations in the DPD gene. Clin. Cancer Res. 6, 4705–4712.

    PubMed  Google Scholar 

  25. Ridge, S.A., Sludden, J., Brown, O., et al. (1998) Dihydropyrimidine dehydrogenase pharma-cogenetics in Caucasian subjects. Br. J. Clin. Pharmacol. 46, 151–156.

    Article  CAS  PubMed  Google Scholar 

  26. Ridge, S.A., Sludden, J., Wei, X., et al. (1998) Dihydropyrimidine dehydrogenase pharmaco-genetics in patients with colorectal cancer. Br. J. Cancer. 77, 497–500.

    Article  CAS  PubMed  Google Scholar 

  27. Johnson, M.R., Wang, K., and Diasio, R.B. (2002) Profound dihydropyrimidine dehydroge-nase deficiency resulting from a novel compound heterozygote genotype. Clin. Cancer Res. 8, 768–774.

    CAS  PubMed  Google Scholar 

  28. Innocenti, F., and Ratain, M.J. (2002) Correspondence re: Raida, M., et al., “Prevalence of a Common Point Mutation in the Dihydropyrimidine Dehydrogenase (DPD) Gene within the 5′-Splice Donor Site of Intron 14 in Patients with Severe 5-Fluorouracil (5-FU)-related Toxicity Compared with Controls,” Clin. Cancer Res. 7, 2832–2839, 2001. Clin. Cancer Res. 8, 1314–1316.

    Google Scholar 

  29. Beutler, E., Gelbart, T., and Demina, A. (1998) Racial variability in the UDP-glucuronosyl-transferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc. Natl. Acad. Sci. U. S. A. 95, 8170–8174.

    Article  CAS  PubMed  Google Scholar 

  30. Fertrin, K.Y., Goncalves, M.S., Saad, S.T., et al. (2002) Frequencies of UDP-glucuronosyl-transferase 1 (UGT1A1) gene promoter polymorphisms among distinct ethnic groups from Brazil. Am. J. Med. Genet. 108, 117–119.

    Article  CAS  PubMed  Google Scholar 

  31. Lampe, J.W., Bigler, J., Horner, N.K., et al. (1999) UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics. 9, 341–349.

    Article  CAS  PubMed  Google Scholar 

  32. Wasserman, E., Myara, A., Lokiec, F., et al. (1997) Severe CPT-11 toxicity in patients with Gilbert's syndrome: two case reports. Ann. Oncol. 8, 1049–1051.

    Article  CAS  PubMed  Google Scholar 

  33. Iyer, L., Hall, D., Das, S., et al. (1999) Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism. Clin. Pharmacol. Ther. 65, 576–582.

    Article  CAS  PubMed  Google Scholar 

  34. Raijmakers, M.T., Jansen, P.L., Steegers, E.A., et al. (2000) Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J. Hepatol. 33, 348–351.

    Article  CAS  PubMed  Google Scholar 

  35. Iyer, L., Das, S., Janisch, L., et al. (2002) UGT1A1*28 polymorphism as a determinant of iri-notecan disposition and toxicity. Pharmacogenomics. J. 2, 43–47.

    Article  CAS  PubMed  Google Scholar 

  36. Iyer, L., Janisch, L., Das, S., et al. (2000) UGT1A1 promoter genotype correlates with phar-macokinetics of irinotecan (CPT-11). ASCO 690.

    Google Scholar 

  37. Ando, Y., Saka, H., Ando, M., et al. (2000) Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res. 60, 6921–6926.

    CAS  PubMed  Google Scholar 

  38. Marcuello, E., Altes, A., Menoyo, A., et al. (2004) UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br. J. Cancer. 91, 678–682.

    CAS  PubMed  Google Scholar 

  39. Ando, Y., Ueoka, H., Sugiyama, T., et al. (2002) Polymorphisms of UDP-glucuronosyltrans-ferase and pharmacokinetics of irinotecan. Ther. Drug Monit. 24, 111–116.

    Article  CAS  PubMed  Google Scholar 

  40. Kishi, S., Yang, W., Boureau, B., et al. (2004) Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia. Blood. 103, 67–72.

    Article  CAS  PubMed  Google Scholar 

  41. Evans, W.E. (2004) Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy. Ther. Drug Monit. 26, 186–191.

    Article  CAS  PubMed  Google Scholar 

  42. Armstrong, V.W., Oellerich, M. (2001) New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus, and azathioprine. Clin. Biochem. 34, 9–16.

    Article  CAS  PubMed  Google Scholar 

  43. Corominas, H., Domenech, M., Gonzalez, D., et al. (2000) Allelic variants of the thiopurine S-methyltransferase deficiency in patients with ulcerative colitis and in healthy controls. Am. J. Gastroenterol. 95, 2313–2317.

    Article  CAS  PubMed  Google Scholar 

  44. McLeod, H.L., Siva, C. (2002) The thiopurine S-methyltransferase gene locus–implications for clinical pharmacogenomics. Pharmacogenomics. 3, 89–98.

    Article  CAS  PubMed  Google Scholar 

  45. Krynetski, E.Y., Schuetz, J.D., Galpin, A.J., et al. (1995) A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc. Natl. Acad. Sci. U. S. A. 92, 949–953.

    Article  CAS  PubMed  Google Scholar 

  46. Yates, C.R., Krynetski, E.Y., Loennechen, T., et al. (1997) Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann. Intern. Med. 126, 608–614.

    CAS  PubMed  Google Scholar 

  47. von Ahsen, N., Armstrong, V.W., and Oellerich, M. (2004) Rapid, long-range molecular hap-lotyping of thiopurine S-methyltransferase (TPMT) *3A, *3B, and *3C. Clin. Chem. 50, 1528–1534.

    Article  Google Scholar 

  48. McLeod, H.L., Krynetski, E.Y., Relling, M.V., et al. (2000) Genetic polymorphism of thiopu-rine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia. 14, 567–572.

    Article  CAS  PubMed  Google Scholar 

  49. Coulthard, S.A., Rabello, C., Robson, J., et al. (2000) A comparison of molecular and enzyme-based assays for the detection of thiopurine methyltransferase mutations. Br. J. Haematol. 110, 599–604.

    Article  CAS  PubMed  Google Scholar 

  50. Relling, M.V., Hancock, M.L., Rivera, G.K., et al. (1999) Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J. Natl. Cancer Inst. 91, 2001–2008.

    Article  CAS  PubMed  Google Scholar 

  51. McLeod, H.L., Coulthard, S., Thomas, A.E., et al. (1999) Analysis of thiopurine methyltrans-ferase variant alleles in childhood acute lymphoblastic leukaemia. Br. J. Haematol. 105, 696–700.

    Article  CAS  PubMed  Google Scholar 

  52. Black, A.J., McLeod, H.L., Capell, H.A., et al. (1998) Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Ann. Intern. Med. 129, 716–718.

    CAS  PubMed  Google Scholar 

  53. Stanulla, M., Schaeffeler, E., Flohr, T., et al. (2005) Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA. 293, 1485–1489.

    Article  CAS  PubMed  Google Scholar 

  54. Dervieux, T., Medard, Y., Verpillat, P., et al. (2001) Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine. Leukemia. 15, 1706–1712.

    CAS  PubMed  Google Scholar 

  55. Tavadia, S.M., Mydlarski, P.R., Reis, M.D., et al. (2000) Screening for azathioprine toxicity: a pharmacoeconomic analysis based on a target case. J. Am. Acad. Dermatol. 42, 628–632.

    Article  CAS  PubMed  Google Scholar 

  56. Baker, D.E. (2003) Pharmacogenomics of azathioprine and 6-mercaptopurine in gastroentero-logic therapy. Rev. Gastroenterol. Disord. 3, 150–157.

    PubMed  Google Scholar 

  57. Oh, K.T., Anis, A.H., and Bae, S.C. (2004) Pharmacoeconomic analysis of thiopurine methyl-transferase polymorphism screening by polymerase chain reaction for treatment with azathio-prine in Korea. Rheumatology (Oxford). 43, 156–163.

    Article  CAS  Google Scholar 

  58. Liu, Y., Hu, M. (2000) P-glycoprotein and bioavailability-implication of polymorphism. Clin. Chem. Lab Med. 38, 877–881.

    Article  CAS  PubMed  Google Scholar 

  59. Nauck, M., Stein, U., von Karger, S., et al. (2000) Rapid detection of the C3435T polymorphism of multidrug resistance gene 1 using fluorogenic hybridization probes. Clin. Chem. 46, 1995–1997.

    CAS  PubMed  Google Scholar 

  60. Cascorbi, I., Gerloff, T., Johne, A., et al. (2001) Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin. Pharmacol. Ther. 69, 169–174.

    Article  CAS  PubMed  Google Scholar 

  61. Hoffmeyer, S., Burk, O., von Richter, O., et al. (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. U. S. A. 97, 3473–3478.

    Article  CAS  PubMed  Google Scholar 

  62. Ameyaw, M.M., Regateiro, F., Li, T., et al. (2001) MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics. 11, 217–221.

    Article  CAS  PubMed  Google Scholar 

  63. Kim, R.B., Leake, B.F., Choo, E.F., et al. (2001) Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin. Pharmacol. Ther. 70, 189–199.

    Article  CAS  PubMed  Google Scholar 

  64. Sugiyama, Y., Kato, Y., and Chu, X. (1998) Multiplicity of biliary excretion mechanisms for the camptothecin derivative irinotecan (CPT-11), its metabolite SN-38, and its glucuronide: role of canalicular multispecific organic anion transporter and P-glycoprotein. Cancer Chemother. Pharmacol. 42(suppl), S44–S49.

    Article  CAS  PubMed  Google Scholar 

  65. Mathijssen, R.H., Marsh, S., Karlsson, M.O., et al. (2003) Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin. Cancer Res. 9, 3246–3253.

    CAS  PubMed  Google Scholar 

  66. Bosch, T.M., Huitema, A.D., Doodeman, V.D., et al. (2006) Pharmacogenetic screening of CYP3A and ABCB1 in relation to population pharmacokinetics of docetaxel. Clin. Cancer Res. 12, 5786–5793.

    Article  CAS  PubMed  Google Scholar 

  67. Goh, B.C., Lee, S.C., Wang, L.Z., et al. (2002) Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and geno-typing strategies. J. Clin. Oncol. 20, 3683–3690.

    Article  CAS  PubMed  Google Scholar 

  68. Sparreboom, A., Marsh, S., Mathijssen, R.H., et al. (2004) Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Invest. New Drugs. 22, 285–289.

    Article  CAS  PubMed  Google Scholar 

  69. Illmer, T., Schuler, U.S., Thiede, C., et al. (2002) MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. Cancer Res. 62, 4955–4962.

    CAS  PubMed  Google Scholar 

  70. Goreva, O.B., Grishanova, A.Y., Mukhin, O.V., et al. (2003) Possible prediction of the efficiency of chemotherapy in patients with lymphoproliferative diseases based on MDR1 gene G2677T and C3435T polymorphisms. Bull. Exp. Biol. Med. 136, 183–185.

    Article  CAS  PubMed  Google Scholar 

  71. Kafka, A., Sauer, G., Jaeger, C., et al. (2003) Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer. Int. J. Oncol. 22, 1117–1121.

    CAS  PubMed  Google Scholar 

  72. Efferth, T., Sauerbrey, A., Steinbach, D., et al. (2003) Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene MDR1 in acute lymphoblastic leukemia. Int. J. Oncol. 23, 509–517.

    CAS  PubMed  Google Scholar 

  73. Kruijtzer, C.M., Beijnen, J.H., Rosing, H., et al. (2002) Increased oral bioavailability of topo-tecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J. Clin. Oncol. 20, 2943–2950.

    Article  CAS  PubMed  Google Scholar 

  74. Zamber, C.P., Lamba, J.K., Yasuda, K., et al. (2003) Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics. 13, 19–28.

    Article  CAS  PubMed  Google Scholar 

  75. Backstrom, G., Taipalensuu, J., Melhus, H., et al. (2003) Genetic variation in the ATP-binding Cassette Transporter gene ABCG2 (BCRP) in a Swedish population. Eur. J. Pharm. Sci. 18, 359–364.

    Article  CAS  PubMed  Google Scholar 

  76. Bosch, T.M., Kjellberg, L.M., Bouwers, A., et al. (2005) Detection of SNPs in the ABCG2 gene in a Dutch population. Am. J. Pharmacogenomics. 5, 123–131.

    Article  CAS  PubMed  Google Scholar 

  77. Mizuarai, S., Aozasa, N., and Kotani, H. (2004) Single nucleotide polymorphisms result in impaired membrane localization and reduced atpase activity in multidrug transporter ABCG2. Int. J. Cancer. 109, 238–246.

    Article  CAS  PubMed  Google Scholar 

  78. Imai, Y., Nakane, M., Kage, K., et al. (2002) C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Mol. Cancer Ther. 1, 611–616.

    CAS  PubMed  Google Scholar 

  79. Sparreboom, A., Gelderblom, H., Marsh, S., et al. (2004) Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype. Clin. Pharmacol. Ther. 76, 38–44.

    Article  CAS  PubMed  Google Scholar 

  80. de Jong, F.A., Marsh, S., Mathijssen, R.H., et al. (2004) ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clin. Cancer Res. 10, 5889–5894.

    Article  PubMed  Google Scholar 

  81. Gottesman, M.M., Fojo, T., and Bates, S.E. (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer. 2, 48–58.

    Article  CAS  PubMed  Google Scholar 

  82. van den Heuvel-Eibrink MM, Wiemer, E.A., Prins, A., et al. (2002) Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML). Leukemia. 16, 833–839.

    Article  PubMed  Google Scholar 

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  1. Medical Center Rijnmond-Zuid, Clinical Pharmacy & Toxicology, Rotterdam, The Netherlands

    Tessa M. Bosch

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  1. PharmTao, Santa Clara, CA, USA

    Qing Yan

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Bosch, T.M. (2008). Pharmacogenomics of Drug-Metabolizing Enzymes and Drug Transporters in Chemotherapy. In: Yan, Q. (eds) Pharmacogenomics in Drug Discovery and Development. Methods in Molecular Biology™, vol 448. Humana Press. https://doi.org/10.1007/978-1-59745-205-2_5

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  • DOI: https://doi.org/10.1007/978-1-59745-205-2_5

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  • Print ISBN: 978-1-58829-887-4

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