Cancer and Metastasis Reviews

, Volume 26, Issue 1, pp 183–201

Pharmacogenetics/genomics of membrane transporters in cancer chemotherapy

Article

Abstract

Inter-individual variability in drug response and the emergence of adverse drug reactions are main causes of treatment failure in cancer therapy. Recently, membrane transporters have been recognized as an important determinant of drug disposition, thereby affecting chemosensitivity and -resistance. Genetic factors contribute to inter-individual variability in drug transport and targeting. Therefore, pharmacogenetic studies of membrane transporters can lead to new approaches for optimizing cancer therapy. This review discusses genetic variations in efflux transporters of the ATP-binding cassette (ABC) family such as ABCB1 (MDR1, P-glycoprotein), ABCC1 (MRP1), ABCC2 (MRP2) and ABCG2 (BCRP), and uptake transporters of the solute carrier (SLC) family such as SLC19A1 (RFC1) and SLCO1B1 (SLC21A6), and their relevance to cancer chemotherapy. Furthermore, a pharmacogenomic approach is outlined, which using correlations between the growth inhibitory potency of anticancer drugs and transporter gene expression in multiple human cancer cell lines, has shown promise for determining the relevant transporters for any given drugs and predicting anticancer drug response.

Keywords

Membrane transporter ABC transporter SLC transporter Chemosensitivity Pharmacogenomics 

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References

  1. 1.
    Cheok, M. H., & Evans, W. E. (2006). Acute lymphoblastic leukaemia: A model for the pharmacogenomics of cancer therapy. Nature Reviews Cancer, 6, 117–129.PubMedCrossRefGoogle Scholar
  2. 2.
    Bodo, A., Bakos, E., Szeri, F., Varadi, A., & Sarkadi, B. (2003). The role of multidrug transporters in drug availability, metabolism and toxicity. Toxicology Letters, 140–141, 133–143.PubMedCrossRefGoogle Scholar
  3. 3.
    Anderle, P., Huang, Y., & Sadee, W. (2004). Intestinal membrane transport of drugs and nutrients: Genomics of membrane transporters using expression microarrays. European Journal of Pharmaceutical Sciences, 21, 17–24.PubMedCrossRefGoogle Scholar
  4. 4.
    Huang, Y., & Sadee, W. (2006). Membrane transporters and channels in chemoresistance and -sensitivity of tumor cells. Cancer Letter, 239, 168–182.CrossRefGoogle Scholar
  5. 5.
    Gottesman, M. M., Fojo, T., & Bates, S. E. (2002). Multidrug resistance in cancer: Role of ATP-dependent transporters. Nature Reviews Cancer, 2, 48–58.PubMedCrossRefGoogle Scholar
  6. 6.
    Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., et al. (2001). The sequence of the human genome. Science, 291, 1304–1351.PubMedCrossRefGoogle Scholar
  7. 7.
    Dean, M., Rzhetsky, A., & Allikmets, R. (2001). The human ATP-binding cassette (ABC) transporter superfamily. Genome Research, 11, 1156–1166.PubMedCrossRefGoogle Scholar
  8. 8.
    Ross, D. D., & Doyle, L. A. (2004). Mining our ABCs: Pharmacogenomic approach for evaluating transporter function in cancer drug resistance. Cancer Cell, 6, 105–107.PubMedCrossRefGoogle Scholar
  9. 9.
    Rabow, A. A., Shoemaker, R. H., Sausville, E. A., & Covell, D. G. (2002). Mining the National Cancer Institute’s tumor-screening database: Identification of compounds with similar cellular activities. Journal of Medicinal Chemistry, 45, 818–840.PubMedCrossRefGoogle Scholar
  10. 10.
    Kim, D. H., Park, J. Y., Sohn, S. K., Lee, N. Y., Baek, J. H., Jeon, S. B., et al. (2006). Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia. International Journal of Cancer, 118, 2195–2201.CrossRefGoogle Scholar
  11. 11.
    Wada, M. (2006). Single nucleotide polymorphisms in ABCC2 and ABCB1 genes and their clinical impact in physiology and drug response. Cancer Letter, 234, 40–50.CrossRefGoogle Scholar
  12. 12.
    Cordon-Cardo, C., O’Brien, J. P., Casals, D., Rittman-Grauer, L., Biedler, J. L., Melamed, M. R., et al. (1989). Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood–brain barrier sites. Proceedings of the National Academy of Sciences of the United States of America, 86, 695–698.PubMedCrossRefGoogle Scholar
  13. 13.
    Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M. M., Pastan, I., & Willingham, M. C. (1987). Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proceedings of the National Academy of Sciences of the United States of America, 84, 7735–7738.PubMedCrossRefGoogle Scholar
  14. 14.
    Schuetz, E. G., Furuya, K. N., & Schuetz, J. D. (1995). Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. Journal of Pharmacology and Experimental Therapeutics, 275, 1011–1018.PubMedGoogle Scholar
  15. 15.
    Schwab, M., Eichelbaum, M., & Fromm, M. F. (2003). Genetic polymorphisms of the human MDR1 drug transporter. Annual Review of Pharmacology and Toxicology, 43, 285–307.PubMedCrossRefGoogle Scholar
  16. 16.
    Marzolini, C., Paus, E., Buclin, T., & Kim, R. B. (2004). Polymorphisms in human MDR1 (P-glycoprotein): Recent advances and clinical relevance. Clinical Pharmacology and Therapeutics, 75, 13–33.PubMedCrossRefGoogle Scholar
  17. 17.
    Cascorbi, I. (2006). Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs. Pharmacology & Therapeutics.Google Scholar
  18. 18.
    Pauli-Magnus, C., & Kroetz, D. L. (2004). Functional implications of genetic polymorphisms in the multidrug resistance gene MDR1 (ABCB1). Pharmaceutical Research, 21, 904–913.PubMedCrossRefGoogle Scholar
  19. 19.
    Stein, U., Walther, W., & Wunderlich, V. (1994). Point mutations in the mdr1 promoter of human osteosarcomas are associated with in vitro responsiveness to multidrug resistance relevant drugs. European Journal of Cancer, 30A, 1541–1545.PubMedCrossRefGoogle Scholar
  20. 20.
    Stein, U., Walther, W., & Shoemaker, R. H. (1996). Vincristine induction of mutant and wild-type human multidrug-resistance promoters is cell-type-specific and dose-dependent. Journal of Cancer Research and Clinical Oncology, 122, 275–282.PubMedCrossRefGoogle Scholar
  21. 21.
    Rund, D., Azar, I., & Shperling, O. (1999). A mutation in the promoter of the multidrug resistance gene (MDR1) in human hematological malignancies may contribute to the pathogenesis of resistant disease. Advances in Experimental Medicine and Biology, 457, 71–75.PubMedGoogle Scholar
  22. 22.
    Mickley, L. A., Lee, J. S., Weng, Z., Zhan, Z., Alvarez, M., Wilson, W., et al. (1998). Genetic polymorphism in MDR-1: A tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors. Blood, 91, 1749–1756.PubMedGoogle Scholar
  23. 23.
    Takane, H., Kobayashi, D., Hirota, T., Kigawa, J., Terakawa, N., Otsubo, K., et al. (2004). Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene. Journal of Pharmacology and Experimental Therapeutics, 311, 1179–1187.PubMedCrossRefGoogle Scholar
  24. 24.
    Taniguchi, S., Mochida, Y., Uchiumi, T., Tahira, T., Hayashi, K., Takagi, K., et al. (2003). Genetic polymorphism at the 5′ regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon. Molecular Cancer Therapeutics, 2, 1351–1359.PubMedGoogle Scholar
  25. 25.
    Lockhart, A. C., Tirona, R. G., & Kim, R. B. (2003). Pharmacogenetics of ATP-binding cassette transporters in cancer and chemotherapy. Molecular Cancer Therapeutics, 2, 685–698.PubMedGoogle Scholar
  26. 26.
    Hoffmeyer, S., Burk, O., von Richter, O., Arnold, H. P., Brockmoller, J., Johne, A., 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. Proceedings of the National Academy of Sciences of the United States of America, 97, 3473–3478.PubMedCrossRefGoogle Scholar
  27. 27.
    Hitzl, M., Drescher, S., van der Kuip, H., Schaffeler, E., Fischer, J., Schwab, M., et al. (2001). The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics, 11, 293–298.PubMedCrossRefGoogle Scholar
  28. 28.
    Ameyaw, M. M., Regateiro, F., Li, T., Liu, X., Tariq, M., Mobarek, A., et al. (2001). MDR1 pharmacogenetics: Frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics, 11, 217–221.PubMedCrossRefGoogle Scholar
  29. 29.
    Kim, R. B., Leake, B. F., Choo, E. F., Dresser, G. K., Kubba, S. V., Schwarz, U. I., et al. (2001). Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clinical Pharmacology and Therapeutics, 70, 189–199.PubMedCrossRefGoogle Scholar
  30. 30.
    Lee, S. S., Kim, S. Y., Kim, W. Y., Thi-Le, H., Yoon, Y. R., Yea, S. S., et al. (2005). MDR1 genetic polymorphisms and comparison of MDR1 haplotype profiles in Korean and Vietnamese populations. Therapeutic Drug Monitoring, 27, 531–535.PubMedCrossRefGoogle Scholar
  31. 31.
    Kroetz, D. L., Pauli-Magnus, C., Hodges, L. M., Huang, C. C., Kawamoto, M., Johns, S. J., et al. (2003). Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics, 13, 481–494.PubMedCrossRefGoogle Scholar
  32. 32.
    Nakamura, T., Sakaeda, T., Horinouchi, M., Tamura, T., Aoyama, N., Shirakawa, T., et al. (2002). Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clinical Pharmacology and Therapeutics, 71, 297–303.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang, D., Johnson, A. D., Papp, A. C., Kroetz, D. L., & Sadee, W. (2005). Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C>T affects mRNA stability. Pharmacogenetics and Genomics, 15, 693–704.PubMedGoogle Scholar
  34. 34.
    Chen, G., Duran, G. E., Steger, K. A., Lacayo, N. J., Jaffrezou, J. P., Dumontet, C., et al. (1997). Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins. Journal of Biological Chemistry, 272, 5974–5982.PubMedCrossRefGoogle Scholar
  35. 35.
    Kioka, N., Tsubota, J., Kakehi, Y., Komano, T., Gottesman, M. M., Pastan, I., et al. (1989). P-glycoprotein gene (MDR1) cDNA from human adrenal: Normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance. Biochemical and Biophysical Research Communications, 162, 224–231.PubMedCrossRefGoogle Scholar
  36. 36.
    Bonhomme-Faivre, L., Devocelle, A., Saliba, F., Chatled, S., Maccario, J., Farinotti, R., et al. (2004). MDR-1 C3435T polymorphism influences cyclosporine a dose requirement in liver-transplant recipients. Transplantation, 78, 21–25.PubMedCrossRefGoogle Scholar
  37. 37.
    Hitzl, M., Schaeffeler, E., Hocher, B., Slowinski, T., Halle, H., Eichelbaum, M., et al. (2004). Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1). Pharmacogenetics, 14, 309–318.PubMedCrossRefGoogle Scholar
  38. 38.
    Lepper, E. R., Nooter, K., Verweij, J., Acharya, M. R., Figg, W. D., & Sparreboom, A. (2005). Mechanisms of resistance to anticancer drugs: The role of the polymorphic ABC transporters ABCB1 and ABCG2. Pharmacogenomics, 6, 115–138.PubMedCrossRefGoogle Scholar
  39. 39.
    Mathijssen, R. H., de Jong, F. A., van Schaik, R. H., Lepper, E. R., Friberg, L. E., Rietveld, T., et al. (2004). Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. Journal of the National Cancer Institute, 96, 1585–1592.PubMedCrossRefGoogle Scholar
  40. 40.
    Plasschaert, S. L., Groninger, E., Boezen, M., Kema, I., de Vries, E. G., Uges, D., et al. (2004). Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic leukemia. Clinical Pharmacology and Therapeutics, 76, 220–229.PubMedCrossRefGoogle Scholar
  41. 41.
    Puisset, F., Chatelut, E., Dalenc, F., Busi, F., Cresteil, T., Azema, J., et al. (2004). Dexamethasone as a probe for docetaxel clearance. Cancer Chemotherapy and Pharmacology, 54, 265–272.PubMedCrossRefGoogle Scholar
  42. 42.
    Tanabe, M., Ieiri, I., Nagata, N., Inoue, K., Ito, S., Kanamori, Y., et al. (2001). Expression of P-glycoprotein in human placenta: Relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. Journal of Pharmacology and Experimental Therapeutics, 297, 1137–1143.PubMedGoogle Scholar
  43. 43.
    Wu, X., Gu, J., Wu, T. T., Swisher, S. G., Liao, Z., Correa, A. M., et al. (2006). Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. Journal of Clinical Oncology, 24, 3789–3798.PubMedCrossRefGoogle Scholar
  44. 44.
    Sai, K., Kaniwa, N., Itoda, M., Saito, Y., Hasegawa, R., Komamura, K., et al. (2003). Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype-dependent renal clearance of irinotecan. Pharmacogenetics, 13, 741–757.PubMedCrossRefGoogle Scholar
  45. 45.
    Mathijssen, R. H., Marsh, S., Karlsson, M. O., Xie, R., Baker, S. D., Verweij, J., et al. (2003). Irinotecan pathway genotype analysis to predict pharmacokinetics. Clinical Cancer Research, 9, 3246–3253.PubMedGoogle Scholar
  46. 46.
    Stanulla, M., Schaffeler, E., Arens, S., Rathmann, A., Schrauder, A., Welte, K., et al. (2005). GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute lymphoblastic leukemia. International Journal of Hematology, 81, 39–44.PubMedCrossRefGoogle Scholar
  47. 47.
    Illmer, T., Schuler, U. S., Thiede, C., Schwarz, U. I., Kim, R. B., Gotthard, S., et al. (2002). MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. Cancer Research, 62, 4955–4962.PubMedGoogle Scholar
  48. 48.
    van den Heuvel-Eibrink, M. M., Wiemer, E. A., de Boevere, M. J., van der Holt, B., Vossebeld, P. J., Pieters, R., et al. (2001). MDR1 gene-related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia. Blood, 97, 3605–3611.PubMedCrossRefGoogle Scholar
  49. 49.
    Kafka, A., Sauer, G., Jaeger, C., Grundmann, R., Kreienberg, R., Zeillinger, R., et al. (2003). Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer. International Journal of Oncology, 22, 1117–1121.PubMedGoogle Scholar
  50. 50.
    Green, H., Soderkvist, P., Rosenberg, P., Horvath, G., & Peterson, C. (2006). mdr-1 single nucleotide polymorphisms in ovarian cancer tissue: G2677T/A correlates with response to paclitaxel chemotherapy. Clinical Cancer Research, 12, 854–859.PubMedCrossRefGoogle Scholar
  51. 51.
    Cole, S. P., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., et al. (1992). Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science, 258, 1650–1654.PubMedCrossRefGoogle Scholar
  52. 52.
    Kruh, G. D., & Belinsky, M. G. (2003). The MRP family of drug efflux pumps. Oncogene, 22, 7537–7552.PubMedCrossRefGoogle Scholar
  53. 53.
    Conseil, G., Deeley, R. G., & Cole, S. P. (2005). Polymorphisms of MRP1 (ABCC1) and related ATP-dependent drug transporters. Pharmacogenetics and Genomics, 15, 523–533.PubMedGoogle Scholar
  54. 54.
    Yasui, K., Mihara, S., Zhao, C., Okamoto, H., Saito-Ohara, F., Tomida, A., et al. (2004). Alteration in copy numbers of genes as a mechanism for acquired drug resistance. Cancer Research, 64, 1403–1410.PubMedCrossRefGoogle Scholar
  55. 55.
    Chen, Z. S., Furukawa, T., Sumizawa, T., Ono, K., Ueda, K., Seto, K., et al. (1999). ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Molecular Pharmacology, 55, 921–928.PubMedGoogle Scholar
  56. 56.
    Leslie, E. M., Deeley, R. G., & Cole, S. P. (2001). Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters. Toxicology, 167, 3–23.PubMedCrossRefGoogle Scholar
  57. 57.
    Leslie, E. M., Deeley, R. G., & Cole, S. P. (2005). Multidrug resistance proteins: Role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicology and Applied Pharmacology, 204, 216–237.PubMedCrossRefGoogle Scholar
  58. 58.
    Conrad, S., Kauffmann, H. M., Ito, K., Deeley, R. G., Cole, S. P., & Schrenk, D. (2001). Identification of human multidrug resistance protein 1 (MRP1) mutations and characterization of a G671V substitution. Journal of Human Genetics, 46, 656–663.PubMedCrossRefGoogle Scholar
  59. 59.
    Conrad, S., Kauffmann, H. M., Ito, K., Leslie, E. M., Deeley, R. G., Schrenk, D., et al. (2002). A naturally occurring mutation in MRP1 results in a selective decrease in organic anion transport and in increased doxorubicin resistance. Pharmacogenetics, 12, 321–330.PubMedCrossRefGoogle Scholar
  60. 60.
    Leslie, E. M., Letourneau, I. J., Deeley, R. G., & Cole, S. P. (2003). Functional and structural consequences of cysteine substitutions in the NH2 proximal region of the human multidrug resistance protein 1 (MRP1/ABCC1). Biochemistry, 42, 5214–5224.PubMedCrossRefGoogle Scholar
  61. 61.
    Letourneau, I. J., Deeley, R. G., & Cole, S. P. (2005). Functional characterization of non-synonymous single nucleotide polymorphisms in the gene encoding human multidrug resistance protein 1 (MRP1/ABCC1). Pharmacogenetics and Genomics, 15, 647–657.PubMedGoogle Scholar
  62. 62.
    Wang, Z., Wang, B., Tang, K., Lee, E. J., Chong, S. S., & Lee, C. G. (2005). A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection. Human Molecular Genetics, 14, 2075–2087.PubMedCrossRefGoogle Scholar
  63. 63.
    Wojnowski, L., Kulle, B., Schirmer, M., Schluter, G., Schmidt, A., Rosenberger, A., et al. (2005). NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation, 112, 3754–3762.PubMedCrossRefGoogle Scholar
  64. 64.
    Taniguchi, K., Wada, M., Kohno, K., Nakamura, T., Kawabe, T., Kawakami, M., et al. (1996). A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Research, 56, 4124–4129.PubMedGoogle Scholar
  65. 65.
    Borst, P., & Elferink, R. O. (2002). Mammalian ABC transporters in health and disease. Annual Review of Biochemistry, 71, 537–592.PubMedCrossRefGoogle Scholar
  66. 66.
    Ito, K., Oleschuk, C. J., Westlake, C., Vasa, M. Z., Deeley, R. G., & Cole, S. P. (2001). Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity. Journal of Biological Chemistry, 276, 38108–38114.PubMedGoogle Scholar
  67. 67.
    Liang, X. J., & Aszalos, A. (2006). Multidrug transporters as drug targets. Current Drug Targets, 7, 911–921.PubMedCrossRefGoogle Scholar
  68. 68.
    Hinoshita, E., Uchiumi, T., Taguchi, K., Kinukawa, N., Tsuneyoshi, M., Maehara, Y., et al. (2000). Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas. Clinical Cancer Research, 6, 2401–2407.PubMedGoogle Scholar
  69. 69.
    Borst, P., Zelcer, N., & van de Wetering, K. (2006). MRP2 and 3 in health and disease. Cancer Letter, 234, 51–61.CrossRefGoogle Scholar
  70. 70.
    Dietrich, C. G., de Waart, D. R., Ottenhoff, R., Schoots, I. G., & Elferink, R. P. (2001). Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in MRP2-deficient rats. Molecular Pharmacology, 59, 974–980.PubMedGoogle Scholar
  71. 71.
    Kala, S. V., Neely, M. W., Kala, G., Prater, C. I., Atwood, D. W., Rice, J. S., et al. (2000). The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. Journal of Biological Chemistry, 275, 33404–33408.PubMedCrossRefGoogle Scholar
  72. 72.
    Kartenbeck, J., Leuschner, U., Mayer, R., & Keppler, D. (1996). Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin–Johnson syndrome. Hepatology, 23, 1061–1066.PubMedGoogle Scholar
  73. 73.
    Tsujii, H., Konig, J., Rost, D., Stockel, B., Leuschner, U., & Keppler, D. (1999). Exon–intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin–Johnson syndrome. Gastroenterology, 117, 653–660.PubMedCrossRefGoogle Scholar
  74. 74.
    Suzuki, H., & Sugiyama, Y. (2002). Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): Its impact on drug disposition. Advanced Drug Delivery Reviews, 54, 1311–1331.PubMedCrossRefGoogle Scholar
  75. 75.
    Machida, I., Wakusawa, S., Sanae, F., Hayashi, H., Kusakabe, A., Ninomiya, H., et al. (2005). Mutational analysis of the MRP2 gene and long-term follow-up of Dubin–Johnson syndrome in Japan. Journal of Gastroenterology, 40, 366–370.PubMedCrossRefGoogle Scholar
  76. 76.
    Sugiyama, Y., Kato, Y., & 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 Chemotherapy and Pharmacology, 42(Suppl), S44–S49.PubMedCrossRefGoogle Scholar
  77. 77.
    Ito, S., Ieiri, I., Tanabe, M., Suzuki, A., Higuchi, S., & Otsubo, K. (2001). Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics, 11, 175–184.PubMedCrossRefGoogle Scholar
  78. 78.
    Itoda, M., Saito, Y., Soyama, A., Saeki, M., Murayama, N., Ishida, S., et al. (2002). Polymorphisms in the ABCC2 (cMOAT/MRP2) gene found in 72 established cell lines derived from Japanese individuals: An association between single nucleotide polymorphisms in the 5′-untranslated region and exon 28. Drug Metabolism and Disposition, 30, 363–364.PubMedCrossRefGoogle Scholar
  79. 79.
    Hulot, J. S., Villard, E., Maguy, A., Morel, V., Mir, L., Tostivint, I., et al. (2005). A mutation in the drug transporter gene ABCC2 associated with impaired methotrexate elimination. Pharmacogenetics and Genomics, 15, 277–285.PubMedCrossRefGoogle Scholar
  80. 80.
    Innocenti, F., Undevia, S. D., Chen, P. X., Das, S., Ramirez, J., Dolan, M. E., et al. (2004). Pharmacogenetic analysis of interindividual irinotecan (CPT-11) pharmacokinetic (PK) variability: Evidence for a functional variant of ABCC2. Proceedings of ASCO, 22 abstract 2010.Google Scholar
  81. 81.
    Zamboni, W. C., Ramanathan, R. K., McLeod, H. L., Mani, S., Potter, D. M., Strychor, S., et al. (2006). Disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in relation to ABC transporter genotypes. Investigational New Drugs, 24, 393–401.PubMedCrossRefGoogle Scholar
  82. 82.
    de Jong, F. A., de Jonge, M. J., Verweij, J., & Mathijssen, R. H. (2006). Role of pharmacogenetics in irinotecan therapy. Cancer Letter, 234, 90–106.CrossRefGoogle Scholar
  83. 83.
    Fromm, M. F., Kauffmann, H. M., Fritz, P., Burk, O., Kroemer, H. K., Warzok, R. W., et al. (2000). The effect of rifampin treatment on intestinal expression of human MRP transporters. American Journal of Pathology, 157, 1575–1580.PubMedGoogle Scholar
  84. 84.
    Hinoshita, E., Taguchi, K., Inokuchi, A., Uchiumi, T., Kinukawa, N., Shimada, M., et al. (2001). Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection. Journal of Hepatology, 35, 765–773.PubMedCrossRefGoogle Scholar
  85. 85.
    Doyle, L. A., Yang, W., Abruzzo, L. V., Krogmann, T., Gao, Y., Rishi, A. K., et al. (1998). A multidrug resistance transporter from human MCF-7 breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 95, 15665–15670.PubMedCrossRefGoogle Scholar
  86. 86.
    Doyle, L. A., & Ross, D. D. (2003). Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene, 22, 7340–7358.PubMedCrossRefGoogle Scholar
  87. 87.
    Sarkadi, B., Ozvegy-Laczka, C., Nemet, K., & Varadi, A. (2004). ABCG2—a transporter for all seasons. FEBS Letters, 567, 116–120.PubMedCrossRefGoogle Scholar
  88. 88.
    Burger, H., van Tol, H., Boersma, A. W., Brok, M., Wiemer, E. A., Stoter, G., et al. (2004). Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood, 104, 2940–2942.PubMedCrossRefGoogle Scholar
  89. 89.
    Houghton, P. J., Germain, G. S., Harwood, F. C., Schuetz, J. D., Stewart, C. F., Buchdunger, E., et al. (2004). Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Research, 64, 2333–2337.PubMedCrossRefGoogle Scholar
  90. 90.
    Kusuhara, H., & Sugiyama, Y. (2006). ATP-binding cassette, subfamily G (ABCG family). Pflügers Archiv.Google Scholar
  91. 91.
    Maliepaard, M., Scheffer, G. L., Faneyte, I. F., van Gastelen, M. A., Pijnenborg, A. C., Schinkel, A. H., et al. (2001). Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Research, 61, 3458–3464.PubMedGoogle Scholar
  92. 92.
    Meyer zu Schwabedissen, H. E., Grube, M., Dreisbach, A., Jedlitschky, G., Meissner, K., Linnemann, K., et al. (2006). Epidermal growth factor-mediated activation of the map kinase cascade results in altered expression and function of abcg2 (bcrp). Drug Metabolism and Disposition, 34, 524–533.PubMedCrossRefGoogle Scholar
  93. 93.
    Yanase, K., Tsukahara, S., Mitsuhashi, J., & Sugimoto, Y. (2006). Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development. Cancer Letter, 234, 73–80.CrossRefGoogle Scholar
  94. 94.
    Imai, Y., Nakane, M., Kage, K., Tsukahara, S., Ishikawa, E., Tsuruo, T., 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. Molecular Cancer Therapeutics, 1, 611–616.PubMedGoogle Scholar
  95. 95.
    Kondo, C., Suzuki, H., Itoda, M., Ozawa, S., Sawada, J., Kobayashi, D., et al. (2004). Functional analysis of SNPs variants of BCRP/ABCG2. Pharmaceutical Research, 21, 1895–1903.PubMedCrossRefGoogle Scholar
  96. 96.
    Gardner, E. R., Burger, H., van Schaik, R. H., van Oosterom, A. T., de Bruijn, E. A., Guetens, G., et al. (2006). Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clinical Pharmacology and Therapeutics, 80, 192–201.PubMedCrossRefGoogle Scholar
  97. 97.
    Mizuarai, S., Aozasa, N., & Kotani, H. (2004). Single nucleotide polymorphisms result in impaired membrane localization and reduced atpase activity in multidrug transporter ABCG2. International Journal of Cancer, 109, 238–246.CrossRefGoogle Scholar
  98. 98.
    Kobayashi, D., Ieiri, I., Hirota, T., Takane, H., Maegawa, S., Kigawa, J., et al. (2005). Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug Metabolism and Disposition, 33, 94–101.PubMedCrossRefGoogle Scholar
  99. 99.
    Zamber, C. P., Lamba, J. K., Yasuda, K., Farnum, J., Thummel, K., Schuetz, J. D., 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.PubMedCrossRefGoogle Scholar
  100. 100.
    Sparreboom, A., Gelderblom, H., Marsh, S., Ahluwalia, R., Obach, R., Principe, P., et al. (2004). Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype. Clinical Pharmacology and Therapeutics, 76, 38–44.PubMedCrossRefGoogle Scholar
  101. 101.
    Sparreboom, A., Loos, W. J., Burger, H., Sissung, T. M., Verweij, J., Figg, W. D., et al. (2005). Effect of ABCG2 genotype on the oral bioavailability of topotecan. Cancer Biology and Therapy, 4, 650–658.PubMedCrossRefGoogle Scholar
  102. 102.
    de Jong, F. A., Marsh, S., Mathijssen, R. H., King, C., Verweij, J., Sparreboom, A., et al. (2004). ABCG2 pharmacogenetics: Ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clinical Cancer Research, 10, 5889–5894.PubMedCrossRefGoogle Scholar
  103. 103.
    Ishikawa, T., Sakurai, A., Kanamori, Y., Nagakura, M., Hirano, H., Takarada, Y., et al. (2005). High-speed screening of human ATP-binding cassette transporter function and genetic polymorphisms: New strategies in pharmacogenomics. Methods in Enzymology, 400, 485–510.PubMedGoogle Scholar
  104. 104.
    Tamura, A., Watanabe, M., Saito, H., Nakagawa, H., Kamachi, T., Okura, I., et al. (2006). Functional validation of the genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG2: Identification of alleles that are defective in porphyrin transport. Molecular Pharmacology, 70, 287–296.PubMedGoogle Scholar
  105. 105.
    Honjo, Y., Hrycyna, C. A., Yan, Q. W., Medina-Perez, W. Y., Robey, R. W., van de Laar, A., et al. (2001). Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Research, 61, 6635–6639.PubMedGoogle Scholar
  106. 106.
    Volk, E. L., & Schneider, E. (2003). Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Research, 63, 5538–5543.PubMedGoogle Scholar
  107. 107.
    Hediger, M. A., Romero, M. F., Peng, J. B., Rolfs, A., Takanaga, H., & Bruford, E. A. (2004). The ABCs of solute carriers: Physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflügers Archiv, 447, 465–468.PubMedCrossRefGoogle Scholar
  108. 108.
    Leabman, M. K., Huang, C. C., DeYoung, J., Carlson, E. J., Taylor, T. R., de la Cruz, M., et al. (2003). Natural variation in human membrane transporter genes reveals evolutionary and functional constraints. Proceedings of the National Academy of Sciences of the United States of America, 100, 5896–5901.PubMedCrossRefGoogle Scholar
  109. 109.
    Urban, T. J., Sebro, R., Hurowitz, E. H., Leabman, M. K., Badagnani, I., Lagpacan, L. L., et al. (2006). Functional genomics of membrane transporters in human populations. Genome Research, 16, 223–230.PubMedCrossRefGoogle Scholar
  110. 110.
    Wong, S. C., Proefke, S. A., Bhushan, A., & Matherly, L. H. (1995). Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells. Journal of Biological Chemistry, 270, 17468–17475.PubMedCrossRefGoogle Scholar
  111. 111.
    Rothem, L., Stark, M., Kaufman, Y., Mayo, L., & Assaraf, Y. G. (2004). Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation. Journal of Biological Chemistry, 279, 374–384.PubMedCrossRefGoogle Scholar
  112. 112.
    Worm, J., Kirkin, A. F., Dzhandzhugazyan, K. N., & Guldberg, P. (2001). Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells. Journal of Biological Chemistry, 276, 39990–40000.PubMedCrossRefGoogle Scholar
  113. 113.
    Gifford, A. J., Haber, M., Witt, T. L., Whetstine, J. R., Taub, J. W., Matherly, L. H., et al. (2002). Role of the E45K-reduced folate carrier gene mutation in methotrexate resistance in human leukemia cells. Leukemia, 16, 2379–2387.PubMedCrossRefGoogle Scholar
  114. 114.
    Kaufman, Y., Ifergan, I., Rothem, L., Jansen, G., & Assaraf, Y. G. (2006). Coexistence of multiple mechanisms of PT523 resistance in human leukemia cells harboring 3 reduced folate carrier alleles: Transcriptional silencing, inactivating mutations, and allele loss. Blood, 107, 3288–3294.PubMedCrossRefGoogle Scholar
  115. 115.
    Zhao, R., Assaraf, Y. G., & Goldman, I. D. (1998). A mutated murine reduced folate carrier (RFC1) with increased affinity for folic acid, decreased affinity for methotrexate, and an obligatory anion requirement for transport function. Journal of Biological Chemistry, 273, 19065–19071.PubMedCrossRefGoogle Scholar
  116. 116.
    Ranganathan, P., & McLeod, H. L. (2006). Methotrexate pharmacogenetics: The first step toward individualized therapy in rheumatoid arthritis. Arthritis and Rheumatism, 54, 1366–1377.PubMedCrossRefGoogle Scholar
  117. 117.
    Chango, A., Emery-Fillon, N., de Courcy, G. P., Lambert, D., Pfister, M., Rosenblatt, D. S., et al. (2000). A polymorphism (80G->A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Molecular Genetics and Metabolism, 70, 310–315.PubMedCrossRefGoogle Scholar
  118. 118.
    Laverdiere, C., Chiasson, S., Costea, I., Moghrabi, A., & Krajinovic, M. (2002). Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia. Blood, 100, 3832–3834.PubMedCrossRefGoogle Scholar
  119. 119.
    Dervieux, T., Kremer, J., Lein, D. O., Capps, R., Barham, R., Meyer, G., et al. (2004). Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis. Pharmacogenetics, 14, 733–739.PubMedCrossRefGoogle Scholar
  120. 120.
    Shimasaki, N., Mori, T., Samejima, H., Sato, R., Shimada, H., Yahagi, N., et al. (2006). Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma. Journal of Pediatric Hematology/Oncology, 28, 64–68.PubMedCrossRefGoogle Scholar
  121. 121.
    Whetstine, J. R., Gifford, A. J., Witt, T., Liu, X. Y., Flatley, R. M., Norris, M., et al. (2001). Single nucleotide polymorphisms in the human reduced folate carrier: Characterization of a high-frequency G/A variant at position 80 and transport properties of the His(27) and Arg(27) carriers. Clinical Cancer Research, 7, 3416–3422.PubMedGoogle Scholar
  122. 122.
    Robien, K., Boynton A., Ulrich C.M. (2005) Pharmacogenetics of folate-related drug targets in cancer treatment. Pharmacogenomics, 6, 673–689.PubMedCrossRefGoogle Scholar
  123. 123.
    Whetstine, J. R., Witt, T. L., & Matherly, L. H. (2002). The human reduced folate carrier gene is regulated by the AP2 and sp1 transcription factor families and a functional 61-base pair polymorphism. Journal of Biological Chemistry, 277, 43873–43880.PubMedCrossRefGoogle Scholar
  124. 124.
    Kaufman, Y., Drori, S., Cole, P. D., Kamen, B. A., Sirota, J., Ifergan, I., et al. (2004). Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia. Cancer, 100, 773–782.PubMedCrossRefGoogle Scholar
  125. 125.
    Liu, M., Ge, Y., Payton, S. G., Aboukameel, A., Buck, S., Flatley, R. M., et al. (2006). Transcriptional regulation of the human reduced folate carrier in childhood acute lymphoblastic leukemia cells. Clinical Cancer Research, 12, 608–616.PubMedCrossRefGoogle Scholar
  126. 126.
    Yang, R., Sowers, R., Mazza, B., Healey, J. H., Huvos, A., Grier, H., et al. (2003). Sequence alterations in the reduced folate carrier are observed in osteosarcoma tumor samples. Clinical Cancer Research, 9, 837–844.PubMedGoogle Scholar
  127. 127.
    DeLeve, L. D. (2000). Liver function and hepatotoxicity in cancer. In R. C. J. Bast, et al. (Ed.), Cancer medicine (5th ed.). Hamilton, Ontario: B.C. Decker Inc.Google Scholar
  128. 128.
    Nozawa, T., Minami, H., Sugiura, S., Tsuji, A., & Tamai, I. (2005). Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: In vitro evidence and effect of single nucleotide polymorphisms. Drug Metabolism and Disposition, 33, 434–439.PubMedCrossRefGoogle Scholar
  129. 129.
    Niemi, M., Schaeffeler, E., Lang, T., Fromm, M. F., Neuvonen, M., Kyrklund, C., et al. (2004). High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics, 14, 429–440.PubMedCrossRefGoogle Scholar
  130. 130.
    Nishizato, Y., Ieiri, I., Suzuki, H., Kimura, M., Kawabata, K., Hirota, T., et al. (2003). Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: Consequences for pravastatin pharmacokinetics. Clinical Pharmacology and Therapeutics, 73, 554–565.PubMedCrossRefGoogle Scholar
  131. 131.
    Nozawa, T., Nakajima, M., Tamai, I., Noda, K., Nezu, J., Sai, Y., et al. (2002). Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): Allele frequencies in the Japanese population and functional analysis. Journal of Pharmacology and Experimental Therapeutics, 302, 804–813.PubMedCrossRefGoogle Scholar
  132. 132.
    Tirona, R. G., Leake, B. F., Merino, G., & Kim, R. B. (2001). Polymorphisms in OATP-C: Identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. Journal of Biological Chemistry, 276, 35669–35675.PubMedCrossRefGoogle Scholar
  133. 133.
    Tirona, R. G., Leake, B. F., Wolkoff, A. W., & Kim, R. B. (2003). Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. Journal of Pharmacology and Experimental Therapeutics, 304, 223–228.PubMedCrossRefGoogle Scholar
  134. 134.
    Efferth, T., & Volm, M. (2005). Pharmacogenetics for individualized cancer chemotherapy. Pharmacology & Therapeutics, 107, 155–176.CrossRefGoogle Scholar
  135. 135.
    Gurwitz, D., Lunshof, J. E., & Altman, R. B. (2006). A call for the creation of personalized medicine databases. Nature Reviews Drug Discovery, 5, 23–26.PubMedCrossRefGoogle Scholar
  136. 136.
    Sadee, W., & Dai, Z. (2005). Pharmacogenetics/genomics and personalized medicine. Human Molecular Genetics, 14(2), R207–R214.PubMedCrossRefGoogle Scholar
  137. 137.
    Ulrich, C. M., Robien, K., & McLeod, H. L. (2003). Cancer pharmacogenetics: Polymorphisms, pathways and beyond. Nature Reviews Cancer, 3, 912–920.PubMedCrossRefGoogle Scholar
  138. 138.
    Huang, Y., Anderle, P., Bussey, K. J., Barbacioru, C., Shankavaram, U., Dai, Z., et al. (2004). Membrane transporters and channels: Role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Research, 64, 4294–4301.PubMedCrossRefGoogle Scholar
  139. 139.
    Frank, N. Y., Margaryan, A., Huang, Y., Schatton, T., Waaga-Gasser, A. M., Gasser, M., et al. (2005). ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Research, 65, 4320–4333.PubMedCrossRefGoogle Scholar
  140. 140.
    Huang, Y., Blower, P. E., Yang, C., Barbacioru, C., Dai, Z., Zhang, Y., et al. (2005). Correlating gene expression with chemical scaffolds of cytotoxic agents: Ellipticines as substrates and inhibitors of MDR1. Pharmacogenomics Journal, 5, 112–125.PubMedCrossRefGoogle Scholar
  141. 141.
    Huang, Y., Dai, Z., Barbacioru, C., & Sadee, W. (2005). Cystine-glutamate transporter SLC7A11 in cancer chemosensitivity and chemoresistance. Cancer Research, 65, 7446–7454.PubMedCrossRefGoogle Scholar
  142. 142.
    Dai, Z., Huang, H., Sadee, W., & Blower, P. E. (2006). Chemoinformatics analysis identifies cytotoxic compounds susceptible to chemoresistance mediated by glutathione and cystine/glutamate transport system. Journal of Medicinal Chemistry, submitted.Google Scholar
  143. 143.
    Szakacs, G., Annereau, J. P., Lababidi, S., Shankavaram, U., Arciello, A., Bussey, K. J., et al. (2004). Predicting drug sensitivity and resistance: Profiling ABC transporter genes in cancer cells. Cancer Cell, 6, 129–137.PubMedCrossRefGoogle Scholar
  144. 144.
    Huang, Y., & Sadee, W. (2003). Drug sensitivity and resistance genes in cancer chemotherapy: A chemogenomics approach. Drug Discovery Today, 8, 356–363.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, College of PharmacyWestern University of Health SciencesPomonaUSA

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