Uridine 5́-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy

Future Oncology

Volumn 6, Issue 4, 2010, Pages 563-585

  Ramrez, Jacqueline ^a   Ratain, Mark J ^a   Innocenti, Federico ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

Epirubicin; Flavopiridol; Glucuronidation; Irinotecan; Neutropenia; Raloxifene; Tamoxifen; TAS 103; Uridine 5 diphosphoglucuronosyltransferase; Vorinostat

Indexed keywords

6 [2 (DIMETHYLAMINO)ETHYLAMINO] 3 HYDROXY 7H INDENO[2,1 C]QUINOLIN 7 ONE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; 7 ETHYL 10 HYDROXYCAMPTOTHECIN GLUCURONIDE; CAPECITABINE; DNA TOPOISOMERASE (ATP HYDROLYSING); EPIRUBICIN; FLAVOPIRIDOL; FLUOROURACIL; FOLINIC ACID; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A3; GLUCURONOSYLTRANSFERASE 1A6; GLUCURONOSYLTRANSFERASE 1A7; GLUCURONOSYLTRANSFERASE 1A9; IRINOTECAN; LORAZEPAM; LUCIFERASE; MESSENGER RNA; MYCOPHENOLIC ACID; NORTAMOXIFEN; OXALIPLATIN; OXAZEPAM; RALOXIFENE; TAMOXIFEN; VORINOSTAT; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR;

ADJUVANT THERAPY; ALTERNATIVE MEDICINE; ANOREXIA; ANTINEOPLASTIC ACTIVITY; BLOOD TOXICITY; BONE MARROW DISEASE; BONE MARROW SUPPRESSION; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER RISK; CELL PROLIFERATION; CHRONIC LYMPHATIC LEUKEMIA; COLORECTAL CANCER; CONTINUOUS INFUSION; CUTANEOUS T CELL LYMPHOMA; DEMETHYLATION; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG DNA INTERACTION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG MEGADOSE; DRUG RESPONSE; DRUG TISSUE LEVEL; ENZYME ACTIVITY; ETHNICITY; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL DISEASE; GENE EXPRESSION; GENE FUNCTION; GENETIC POLYMORPHISM; GENETIC SCREENING; GENETIC VARIABILITY; GILBERT DISEASE; GLUCURONIDATION; GYNECOLOGIC CANCER; HAPLOTYPE; HUMAN; ISOMERIZATION; KIDNEY CANCER; KIDNEY METASTASIS; LEUKOPENIA; LOW DRUG DOSE; LUNG SMALL CELL CANCER; MISSENSE MUTATION; MONOTHERAPY; NAUSEA; NEOPLASM; NEUTROPENIA; NEUTROPHIL COUNT; OPTIMAL DRUG DOSE; PHARMACOGENETICS; POSTMENOPAUSE OSTEOPOROSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; RECEPTOR AFFINITY; RECOMMENDED DRUG DOSE; REVIEW; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; RISK REDUCTION; SIDE EFFECT; STOMACH CANCER; TARGET CELL; THERAPY DELAY; THROMBOCYTOPENIA; TREATMENT RESPONSE; ENZYMOLOGY; GENETICS;

ANTINEOPLASTIC AGENTS; ENZYME INHIBITORS; GLUCURONOSYLTRANSFERASE; HUMANS; NEOPLASMS; POLYMORPHISM, GENETIC;

EID: 77950607932     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.10.17     Document Type: Review

References (243)

1. King CD, Rios GR, Green MD, Tephly TR: UDP-glucuronosyltransferases. Curr. Drug Metab. 1(2), 143-161 (2000).
2. Ritter JK: Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reactions. Chem. Biol. Interact. 129(1-2), 171-193 (2000).
3. Fisher MB, Paine MF, Strelevitz TJ, Wrighton SA: The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism. Drug Metab. Rev. 33(3-4), 273-297 (2001).
4. Tukey RH, Strassburg CP: Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu. Rev. Pharmacol. Toxicol. 40, 581-616 (2000).
5. Turgeon D, Carrier JS, Lévesque E, Hum DW, Bélanger A: Relative enzymatic activity, protein stability and tissue distribution of human steroid metabolizing UGT2B subfamily members. Endocrinology 142(2), 778-787 (2001).
6. Finel M, Li X, Gardner-Stephen D, Bratton S, Mackenzie PI, Radominska-Pandya A: Human UDP-glucuronosyltransferase 1A5: identification, expression, and activity. J. Pharmacol. Exp. Ther. 315(3), 1143-1149 (2005).
7. Izukawa T, Nakajima M, Fujiwara R et al.: Quantitative analysis of UDP-glucuronosyltransferase (UGT) 1A and UGT2B expression levels in human livers. Drug Metab. Dispos. 37(8), 1759-1768 (2009).
8. Strassburg CP, Kalthoff S, Ehmer U: Variability and function of family 1 uridine-5́-diphosphate glucuronosyltransferases (UGT1A). Crit. Rev. Clin. Lab. Sci. 45(6), 485-530 (2008).
9. Guillemette C: Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J. 3(3), 136-158 (2003
10. Meyerhardt JA, Mayer RJ: Systemic therapy for colorectal cancer. N. Engl. J. Med. 352(5), 476-487(2005).
11. Catalano V, Labianca R, Beretta GD, Gatta G, De Braud F, Van Cutsem E: Gastric cancer. Crit. Rev. Oncol. Hematol. 71(2), 127-164 (2009).
12. Murphy CG, Seidman AD: Evolving approaches to metastatic breast cancer previously treated with anthracyclines and taxanes. Clin. Breast Cancer 9(Suppl. 2), S58-S65 (2009).
13. Burris HA, Rothenberg ML, Kuhn JG, Von Hoff DD: Clinical trials with the topoisomerase I inhibitors. Semin. Oncol. 19(6), 663-669 (1992).
14. Kawato Y, Aonuma M, Hirota Y, Kuga H, Sato K: Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res. 51(16), 4187-4191(1991).
15. Rivory LP, Robert J: Identification and kinetics of a b-glucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan. Cancer Chemother. Pharmacol. 36(2), 176-179 (1995).
16. Iyer L, King CD, Whitington PF et al.: Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J. Clin. Invest. 101(4), 847-854 (1998).
17. Hanioka N, Ozawa S, Jinno H, Ando M, Saito Y, Sawada J: Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin. Xenobiotica 31(10), 687-699 (2001).
18. Gagne JF, Montminy V, Belanger P et al.: Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10- hydroxycamptothecin (SN-38). Mol. Pharmacol. 62(3), 608-617 (2002).
19. Ciotti M, Basu N, Brangi M, Owens IS: Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus. Biochem. Biophys. Res. Commun. 260(1), 199-202 (1999).
20. Tallman MN, Ritter JK, Smith, PC: Differential rates of glucuronidation for 7-ethyl-10-hydroxy-camptothecin (SN-38) lactone and carboxylate in human and rat microsomes and recombinant UDP-glucuronosyltransferase isoforms. Drug Metab. Dispos. 33(7), 977-983 (2005).
21. Yong WP, Ramirez J, Innocenti F, Ratain MJ: Effects of ketoconazole on glucuronidation by UDP-glucuronosyltransferase enzymes. Clin. Cancer Res. 11(18), 6699-6704 (2005).
22. Lankisch TO, Vogel A, Eilermann S et al.: Identification and characterization of a functional TATA box polymorphism of the UDP glucuronosyltransferase 1A7 gene. Mol. Pharmacol. 67(5), 1732-1739 (2005).
23. Guillemette C, Ritter JK, Auyeung DJ, Kessler FK, Housman DE: Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene. Pharmacogenetics 10(7), 629-644 (2000).
24. Tukey RH, Strassburg CP: Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract. Mol. Pharmacol. 59(3), 405-414 (2001
25. Zheng Z, Fang JL, Lazarus P: Glucuronidation: an important mechanism for detoxification of benzo[A]pyrene metabolites in aerodigestive tract tissues. Drug Metab. Dispos. 30(4), 397-403 (2002).
26. Wasserman E, Myara A, Lokiec F et al.: Severe CPT-11 toxicity in patients with Gilbert's syndrome: two case reports. Ann. Oncol. 8(10), 1049-1051 (1997).
27. Wasserman E, Cuvier C, Lokiec F et al.: Combination of oxaliplatin plus irinotecan in patients with gastrointestinal tumors: results of two independent Phase I studies with pharmacokinetics. J. Clin. Oncol. 17(6), 1751-1759 (1999).
28. Bosma PJ, Chowdhury RJ, Bakker C et al.: The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N. Engl. J. Med. 333(18), 1171-1175 (1995).
29. Iyer L, Hall D, Das S et al.: 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(5), 576-582 (1999).
30. Innocenti F, Grimsley C, Das S et al.: Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups. Pharmacogenetics 12(9), 725-733 (2002).
31. Iyer L, Das S, Janisch L et al.: UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J. 2(1), 43-47 (2002).
32. Innocenti F, Undevia SD, Iyer L et al.: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J. Clin. Oncol. 22(8), 1382-1388 (2004).
33. Ramírez J, Mirkov S, Zhang W et al.: Hepatocyte nuclear factor-1 a is associated with UGT1A1, UGT1A9 and UGT2B7 mRNA expression in human liver. Pharmacogenomics J. 8(2), 152-161 (2008).
34. Rouits E, Boisdron-Celle M, Dumont A, Guerin O, Morel A, Gamelin E: Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients. Clin. Cancer Res. 10(15), 5151-5159 (2004).
35. McLeod HL, Parodi L, Sargent DJ et al.: UGT1A1*28, toxicity and outcome in advanced colorectal cancer: results from trial N9741. Presented at: American Society of Clinical Oncology (ASCO) 2006 Annual Meeting. Atlanta, GA, USA, 2-6 June (2006).
36. Toffoli G, Cecchin E, Corona G et al.: The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. J. Clin. Oncol. 24(19), 3061-3068 (2006).
37. Côté JF, Kirzin S, Kramar A et al.: UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Clin. Cancer Res. 13(11), 3269-3275 (2007).
38. Capitain O, Asevoaia A, Boisdron-Celle M et al.: Influence of pharmacogenetic polymorphisms on 5-fluorouracil and irinotecan efficacy and tolerance in patients treated for advanced colorectal cancer. Presented at: 2008 Gastrointestinal Cancers Symposium. Orlando, FL, USA, 25-28 January (2008).
39. Ando Y, Saka H, Ando M et al.: Polymorphisms of UDP- glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res. 60(24), 6921-6926 (2000).
40. Kitagawa C, Ando M, Ando Y et al.: Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity. Pharmacogenet. Genomics 15(1), 35-41 (2005).
41. Yamamoto N, Takahashi T, Kunihane H et al.: Phase I/II pharmacokinetic and pharmacogenomic study of UGT1A1 polymorphism in elderly patients with advanced non-small cell lung cancer treated with irinotecan. Clin. Pharmacol. Ther. 85(2), 149-154 (2009).
42. Minami H, Sai K, Saeki M et al.: Irinotecan pharmacokinetics/ pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Pharmacogenet. Genomics 17(7), 497-504 (2007).
43. Marcuello E, Altes A, Menoyo A, Del Rio E, Gomez-Pardo M, Baiget M: UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br. J. Cancer 91(4), 678-682 (2004).
44. De Jong FA, Kehrer DF, Mathijssen RH et al.: Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for UGT1A1*28 genotype screening: a double-blind, randomized, placebo-controlled study. Oncologist 11(8), 944-954 (2006).
45. Massacesi C, Terrazzino S, Marcucci F et al.: Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Cancer 106(5), 1007-1016 (2006).
46. Chiara S, Lastraioli P, Marroni L et al.: Polymorphisms in UGT1A gene family and irinotecan toxicity in patients with advanced colorectal cancer. Presented at: American Society of Clinical Oncology (ASCO) 2006 Annual Meeting. Atlanta, GA, USA, 2-6 June (2006).
47. Carlini LE, Meropol NJ, Bever J et al.: UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/ irinotecan. Clin. Cancer Res. 11(3), 1226-1236 (2005).
48. Han JY, Lim HS, Shin ES et al.: Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J. Clin. Oncol. 24(15), 2237-2244 (2006).
49. Han J, Lee S, Lee D, Kim H, Lee J: Pharmacogenetic prediction for tumor response, toxicity, and survival of NSCLC patients treated with irinotecan and cisplatin chemotherapy. Presented at: American Society of Clinical Oncology (ASCO) 2007 Annual Meeting. Chicago, IL, USA, 1-5 June (2007).
50. Soepenberg O, Dumez H, Verweij J et al.: Phase I pharmacokinetic, food effect, and pharmacogenetic study of oral irinotecan given as semisolid matrix capsules in patients with solid tumors. Clin. Cancer Res. 11(4), 1504-1511 (2005). (Pubitemid 40315233)
51. Font A, Sanchez JM, Taron M et al.: Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung cancer patients and correlation with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism. Invest. New Drugs 21(4), 435-443 (2003).
52. Singh L, Singh AS, Price DK et al.: Influence of genetic variants in UGT1A1 and UGT1A9 on the in vivo glucuronidation of SN-38. J. Clin. Pharmacol. 44(8), 854-860 (2004).
53. Singh A, Paoluzzi L, Price D et al.: Influence of genetic variants in UGT1A1 and UGT1A9 on the in vivo glucuronidation of SN-38. Presented at: American Society of Clinical Oncology (ASCO) 2004 Annual Meeting. New Orleans, LA, USA, 5-8 June (2004).
54. De Jong FA, Scott-Horton TJ, Kroetz DL et al.: Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein. Clin. Pharmacol. Ther. 81(1), 42-49 (2007).
55. Hoskins JM, Goldberg RM, Qu P, Ibrahim JG, McLeod HL: UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J. Natl Cancer Inst. 99(17), 1290-1295 (2007).
56. Saito Y, Maekawa K, Ozawa S, Sawada J: Genetic polymorphisms and haplotypes of major drug metabolizing enzymes in East Asians and their comparison with other ethnic populations. Curr. Pharmacogenomics 5(1), 49-78 (2007).
57. Yamamoto K, Sato H, Fujiyama Y, Doida Y, Bamba T: Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP-glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II. Biochim. Biophys. Acta. 1406(3), 267-273 (1998).
58. Jinno H, Saeki M, Saito Y et al.: Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients. J. Pharmacol. Exp. Ther. 306(2), 688-693 (2003).
59. Jada SR, Lim R, Wong CI et al.: Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci. 98(9), 1461-1467 (2007).
60. Hazama S, Okuyama Y, Kato T et al.: Use of genotype subset selections of multi-UGT1As polymorphisms to predict severe neutropenia and tumor responses of metastatic CRC patients received FOLFIRI regimen. Presented at: American Society of Clinical Oncology (ASCO) 2009 Annual Meeting. Orlando, FL, USA, 29 May-2 June (2009).
61. Hsieh SY, Wu YH, Lin DY, Chu CM, Wu M, Liaw YF: Correlation of mutational analysis to clinical features in Taiwanese patients with Gilbert's syndrome. Am. J. Gastroenterol. 96(4), 1188-1193 (2001).
62. Sai K, Saeki M, Saito Y et al.: UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer. Clin. Pharmacol. Ther. 75(6), 501-515 (2004).
63. Araki K, Fujita K, Ando Y et al.: Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene on SN-38 glucuronidation in Japanese patients with cancer. Cancer Sci. 97(11), 1255-1259 (2006).
64. Sai K, Saito Y, Sakamoto H et al.: Importance of UDP- glucuronosyltransferase 1A1*6 for irinotecan toxicities in Japanese cancer patients. Cancer Lett. 261(2), 165-171 (2008).
65. Innocenti F, Ratain MJ: Pharmacogenetics of irinotecan: clinical perspectives on the utility of genotyping. Pharmacogenomics 7(8), 1211-1221 (2006).
66. Sai K, Saito Y, Maekawa K et al.: Additive effects of drug transporter genetic polymorphisms on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients. Cancer Chemother. Pharmacol. DOI: 10.1007/s00280-009- 1138-y (2009) (Epub ahead of print).
67. Kaniwa N, Kurose K, Jinno H et al.: Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C>T (P229L) found in an African-American. Drug Metab. Dispos. 33(3), 458-465 (2005).
68. Innocenti F, Liu W, Chen P, Desai AA, Das S, Ratain MJ: Haplotypes of variants in the UDP-glucuronosyltransferase 1A9 and 1A1 genes. Pharmacogenet. Genomics 15(5), 295-301 (2005).
69. Lara Jr P, Redman M, Lenz H et al.: Cisplatin (Cis)/etoposide (VP16) compared with cis/irinotecan (CPT-11) in extensive-stage small cell lung cancer (E-SCLC): pharmacogenomic (PG) and comparative toxicity analysis of JCOG 9511 and SWOG 0124. Presented at: American Society of Clinical Oncology (ASCO) 2007 Annual Meeting. Chicago, IL, USA, 1-5 June (2007).
70. Cecchin E, Innocenti F, D'Andrea M et al.: Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan. J. Clin. Oncol. 27(15), 2457-2465 (2009).
71. Sugatani J, Yamakawa K, Yoshinari K et al.: Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochem. Biophys. Res. Commun. 292(2), 492-497 (2002).
72. Yamanaka H, Nakajima M, Katoh M et al.: A novel polymorphism in the promoter region of human UGT1A9 gene (UGT1A9*22) and its effects on the transcriptional activity. Pharmacogenetics 14(5), 329-332 (2004).
73. Girard H, Villeneuve L, Court MH et al.: The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver. Drug Metab. Dispos. 34(7), 1220-1228 (2006).
74. Girard H, Court MH, Bernard O et al.: Identification of common polymorphisms in the promoter of the UGT1A9 gene: evidence that UGT1A9 protein and activity levels are strongly genetically controlled in the liver. Pharmacogenetics 14(8), 501-515 (2004).
75. Ramírez J, Liu W, Mirkov S et al.: Lack of association between common polymorphisms in UGT1A9 and gene expression and activity. Drug Metab. Dispos. 35(12), 2149-2153 (2007).
76. Inoue K, Miura M, Satoh S et al.: Influence of UGT1A7 and UGT1A9 intronic I399 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Ther. Drug Monit. 29(3), 299-304 (2007). (Pubitemid 47262259)
77. Huang MJ, Yang SS, Lin MS, Huang CS: Polymorphisms of uridine-diphosphoglucuronosyltransferase 1A7 gene in Taiwan Chinese. World J. Gastroenterol. 11(6), 797-802 (2005).
78. Lankisch TO, Schulz C, Zwingers T et al.: Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Cancer Epidemiol. Biomarkers Prev. 17(3), 695-701 (2008).
79. Kohle C, Mohrle B, Munzel PA et al.: Frequent co-occurrence of the TATA box mutation associated with Gilbert's syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians. Biochem. Pharmacol. 65(9), 1521-1527 (2003).
80. Villeneuve L, Girard H, Fortier LC, Gagné JF, Guillemette C: Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs. J. Pharmacol. Exp. Ther. 307(1), 117-128 (2003).
81. Saeki M, Saito Y, Jinno H et al.: Haplotype structures of the UGT1A gene complex in a Japanese population. Pharmacogenomics J. 6(1), 63-75 (2006).
82. Fujita KI, Ando Y, Nagashima F et al.: Genetic linkage of UGT1A7 and UGT1A9 polymorphisms to UGT1A1*6 is associated with reduced activity for SN-38 in Japanese patients with cancer. Cancer Chemother. Pharmacol. 60(4), 515-522 (2007).
83. Saito Y, Sai K, Maekawa K et al.: Close association of UGT1A9 IVS1399C>T with UGT1A1*28, *6, or *60 haplotype and its apparent influence on 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation in Japanese. Drug Metab. Dispos. 37(2), 272-276 (2009).
84. Mathijssen RH, De Jong FA, Van Schaik RH et al.: Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J. Natl. Cancer Inst. 96 (21), 1582-1592 (2004).
85. Paoluzzi L, Singh AS, Price DK et al.: Influence of genetic variants in UGT1A1 and UGT1A9 on the in vivo glucuronidation of SN-38. J. Clin. Pharmacol. 44(8), 854-860 (2004).
86. Kohle C, Mohrle B, Munzel PA et al.: Frequent co-occurrence of the TATA box mutation associated with Gilbert's syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians. Biochem. Pharmacol. 65(9), 1521-1527 (2003).
87. Sandanaraj E, Jada SR, Shu X et al.: Influence of UGT1A9 intronic I399C>T polymorphism on SN-38 glucuronidation in Asian cancer patients. Pharmacogenomics J. 8(3), 174-185 (2008).
88. Rouits E, Charasson V, Pétain A et al.: Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients. Br. J. Cancer 99(8), 1239-1245 (2008).
89. Slatter JG, Schaaf LJ, Sams JP et al.: Pharmacokinetics, metabolism, and excretion of irinotecan (CPT-11) following i.v. infusion of [(14)C]CPT-11 in cancer patients. Drug Metab. Dispos. 28, 423-433 (2000).
90. Innocenti F, Vokes EE, Ratain MJ: Irinogenetics: what is the right star? J. Clin. Oncol. 24(15), 2221-2224 (2006).
91. Kim TW, Innocenti F: Insights, challenges and future directions in irinogenetics. Ther. Drug. Monit. 29(3), 265-270 (2007).
92. Toffoli G, Cecchin E, Gasparini G et al.: Genotype driven Phase-1 study of irinotecan administered in combination with 5-fluorouracil/leucovorin (FOLFIRI) in metastatic colorectal cancer patients. J. Clin. Oncol. 28(5), 866-871 (2010).
93. Innocenti F, Janisch L, Das S et al.: A genotype-directed Phase I study of irinotecan in advanced cancer patients. Presented at: American Society of Clinical Oncology (ASCO) 2007 Annual Meeting. Chicago, IL, USA, 1-5 June (2007).
94. Kim T, Sym S, Lee S et al.: A UGT1A1 genotype-directed Phase I study of irinotecan (CPT-11) combined with fixed dose of capecitabine in patients with metastatic colorectal cancer (mCRC). Presented at: American Society of Clinical Oncology (ASCO) 2009 Annual Meeting. Orlando, FL, USA, 29 May-2 June (2009).
95. Esaki T, Satoh T, Ura T et al.: A prospective PGx and PK/PD dose-finding study of irinotecan based on UGT1A1*6 and *28 genotyping (UGT0601). Presented at: American Society of Clinical Oncology (ASCO) 2009 Annual Meeting. Orlando, FL, USA, 29 May-2 June (2009).
96. Jordan VC: Tamoxifen: the herald of a new era of preventive therapeutics. J. Natl Cancer Inst. 89(11), 747-749 (1997).
97. Osborne CK: Tamoxifen in the treatment of breast cancer. N. Engl. J. Med. 339(22), 1609-1618 (1998).
98. Cuzick J, Powles T, Veronesi U et al.: Overview of the main outcomes in breast-cancer prevention trials. Lancet 361(9354), 296-300 (2003).
99. Boocock DJ, Brown K, Gibbs AH, Sanchez E, Turteltaub KW, White IN: Identification of human CYP forms involved in the activation of tamoxifen and irreversible binding to DNA. Carcinogenesis 23(11), 1897-1901 (2002).
100. Kim SY, Suzuki N, Santosh Laxmi YR, Rieger R, Shibutani S: a-hydroxylation of tamoxifen and toremifene by human and rat cytochrome P450 3A subfamily enzymes. Chem. Res. Toxicol. 16(9), 1138-1144 (2003).
101. Desta Z, Ward BA, Soukhova NV, Flockhart DA: Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J. Pharmacol. Exp. Ther. 310(3), 1062-1075 (2004).
102. Jacolot F, Simon I, Dreano Y, Beaune P, Riche C, Berthou F: Identification of the cytochrome P450 IIIA family as the enzymes involved in the N-demethylation oftamoxifen in human liver microsomes. Biochem. Pharmacol. 41(12), 1911-1919 (1991).
103. Crewe HK, Ellis SW, Lennard MS, Tucker GT: Variable contribution of cytochromes P450 2D6, 2C9 and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes. Biochem. Pharmacol. 53(2), 171-178 (1997).
104. Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4́-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab. Dispos. 30(8), 869-874 (2002).
105. Hu Y, Dehal SS, Hynd G, Jones GB, Kupfer D: CYP2D6-mediated catalysis of tamoxifen aromatic hydroxylation with an NIH shift: similar hydroxylation mechanism in chicken, rat and human liver microsomes. Xenobiotica 33(2), 141-151 (2003).
106. Dehal SS, Kupfer D: CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res. 57(16), 3402-3406 (1997).
107. Coller JK: Oxidative metabolism of tamoxifen to Z-4-hydroxy-tamoxifen by cytochrome P450 isoforms: an appraisal of in vitro studies. Clin. Exp. Pharmacol. Physiol. 30(11), 845-848 (2003).
108. Coller JK, Krebsfaenger N, Klein K et al.: Large interindividual variability in the in vitro formation of tamoxifen metabolites related to the development of genotoxicity. Br. J. Clin Pharmacol. 57(1), 105-111 (2004). (Pubitemid 38067957)
109. Stearns V, Johnson MD, Rae JM et al.: Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J. Natl Cancer Inst. 95(23), 1758-1764 (2003). (Pubitemid 38008898)
110. Lien EA, Solheim E, Kvinnsland S, Ueland PM: Identification of 4-hydroxy-N-desmethyltamoxifen as a metabolite of tamoxifen in human bile. Cancer Res. 48(8), 2304-2308 (1988).
111. Lien EA, Solheim E, Lea OA, Lundgren S, Kvinnsland S, Ueland PM: Distribution of 4hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer Res. 49(8), 2175-2183 (1989). (Pubitemid 19106533)
112. Poon GK, Chui YC, McCague R et al.: Analysis of Phase I and Phase II metabolites of tamoxifen in breast cancer patients. Drug Metab. Dispos. 21(6), 1119-1124 (1993). (Pubitemid 23348351)
113. Sun D, Sharma AK, Dellinger RW et al.: Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab. Dispos. 35(11), 2006-2014 (2007). (Pubitemid 350010805)
114. Zhao L, Krishnan S, Zhang Y, Schenkman JB, Rusling JF. Differences in metabolite-mediated toxicity of tamoxifen in rodents versus humans elucidated with DNA/microsome electro-optical arrays and nanoreactors. Chem. Res. Toxicol. 22(2), 341-347 (2009).
115. Ogura K, Ishikawa Y, Kaku T et al.: Quaternary ammonium-linked glucuronidation of trans-4-hydroxytamoxifen, an active metabolite of tamoxifen, by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem. Pharmacol. 71(9), 1358-1369 (2006).
116. Nishiyama T, Ogura K, Nakano H et al.: Reverse geometrical selectivity in glucuronidation and sulfation of cis-and trans-4-hydroxytamoxifens by human liver UDP-glucuronosyltransferases and sulfotransferases. Biochem. Pharmacol. 63(10), 1817-1830 (2002). (Pubitemid 34603446)
117. Zheng Y, Sun D, Sharma AK, Chen G, Amin S, Lazarus P: Elimination of antiestrogenic effects of active tamoxifen metabolites by glucuronidation. Drug Metab. Dispos. 35(10), 1942-1948 (2007). (Pubitemid 47481590)
118. Lazarus P, Blevins-Primeau AS, Zheng Y, Sun D: Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen. Ann. NY Acad. Sci. 1155, 99-111 (2009).
119. Blevins-Primeau AS, Sun D, Chen G et al.: Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 69(5), 1892-1900 (2009).
120. Kaku T, Ogura K, Nishiyama T, Ohnuma T, Muro K, Hiratsuka A: Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem. Pharmacol. 67(11), 2093-2102 (2004). (Pubitemid 38595490)
121. Apak TI, Duffel MW: Interactions of the stereoisomers of a-hydroxytamoxifen with human hydroxysteroid sulfotransferase SULT2A1 and rat hydroxysteroid sulfotransferase STa. Drug Metab. Dispos. 32(12), 1501-1508 (2004).
122. Coller JK, Krebsfaenger N, Klein K et al.: The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liver. Br. J. Clin. Pharmacol. 54(2), 157-167 (2002). (Pubitemid 35024939)
123. Lim YC, Desta Z, Flockhart DA, Skaar TC: Endoxifen (4-hydroxy-N- desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen. Cancer Chemother. Pharmacol. 55(5), 471-478 (2005). (Pubitemid 40568978)
124. Katzenellenbogen BS, Norman MJ, Eckert RL, Peltz SW, Mangel WF: Bioactivities, estrogen receptor interactions, and plasminogen activator-inducing activities of tamoxifen and hydroxy-tamoxifen isomers in MCF-7 human breast cancer cells. Cancer Res. 44(1), 112-119 (1984).
125. Furr BJ, Jordan VC: The pharmacology and clinical uses of tamoxifen. Pharmacol. Ther. 25(2), 127-205 (1984).
126. Johnson MD, Zuo H, Lee KH et al.: Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res. Treat. 85(2), 151-159 (2004). (Pubitemid 38987269)
127. Jin Y, Desta Z, Stearns V et al.: CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J. Natl Cancer Inst. 97(1), 30-39 (2005).
128. Malet C, Spritzer P, Cumins C, Guillaumin D, Mauvais-Jarvis P, Kuttenn F: Effect of 4-hydroxytamoxifen isomers on growth and ultrastructural aspects of normal human breast epithelial (HBE) cells in culture. J. Steroid Biochem. Mol. Biol. 82(4-5), 289-296 (2002). (Pubitemid 36183183)
129. Sun D, Chen G, Dellinger RW, Duncan K, Fang JL, Lazarus P: Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation by human UGT1A4 variants. Breast Cancer Res. 8(4), R50 (2006). (Pubitemid 44323677)
130. Heringa M: Review on raloxifene: profile of a selective estrogen receptor modulator. Int. J. Clin. Pharmacol. Ther. 41(8), 331-345 (2003). (Pubitemid 36980563)
131. Visvanathan K, Chlebowski RT, Hurley P et al.: American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J. Clin. Oncol. 27(19), 3235-3258 (2009).
132. Vogel VG: The NSABP Study of Tamoxifen and Raloxifene (STAR) trial. Expert Rev. Anticancer Ther. 9(1), 51-60 (2009).
133. Snyder KR, Sparano N, Malinowski JM: Raloxifene hydrochloride. Am J. Health Syst. Pharm. 57(18), 1669-1675(2000).
134. Hochner-Celnikier D: Pharmacokinetics of raloxifene and its clinical application. Eur. J. Obstet. Gynecol. Reprod. Biol. 85(1), 23-29 (1999). (Pubitemid 29248779)
135. Dodge JA, Lugar CW, Cho S et al.: Evaluation of the major metabolites of raloxifene as modulators of tissue selectivity. J. Steroid Biochem. Mol. Biol. 61(1-2), 97-106 (1997). (Pubitemid 27395747)
136. Kemp DC, Fan PW, Stevens JC: Characterization of raloxifene glucuronidation in vitro: contribution of intestinal metabolism to presystemic clearance. Drug Metab. Dispos. 30(6), 694-700 (2002).
137. Jeong EJ, Liu Y, Lin H, Hu M: Species-and disposition model-dependent metabolism of raloxifene in gut and liver: role of UGT1A10. Drug Metab. Dispos. 33(6), 785-794 (2005). (Pubitemid 40686632)
138. Chang JH, Yoo P, Lee T, Klopf W, Takao D: The role of pH in the glucuronidation of raloxifene, mycophenolic acid and ezetimibe. Mol. Pharm. 6(4), 1216-1227 (2009).
139. Trontelj J, Marc J, Zavratnik A, Bogataj M, Mrhar A: Effects of UGT1A1*28 polymorphism on raloxifene pharmacokinetics and pharmacodynamics. Br. J. Clin. Pharmacol. 67(4), 437-444 (2009).
140. Ganzina F: 4́-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data. Cancer Treat Rev. 10(1), 1-22 (1983). (Pubitemid 13058185)
141. Brunello A, Roma A, Falci C, Basso U: Chemotherapy and targeted agents for elderly women with advanced breast cancer. Recent Pat. Anticancer Drug Discov. 3(3), 187-201 (2008).
142. Levine M: Epirubicin in breast cancer: present and future. Clin. Breast Cancer 1(Suppl. 1), S62-S67 (2000).
143. Li YF, Fu S, Hu W et al.: Systemic anticancer therapy in gynecological cancer patients with renal dysfunction. Int. J. Gynecol. Cancer 17(4), 739-763 (2007). (Pubitemid 47063315)
144. Ormrod D, Holm K, Goa K, Spencer C: Epirubicin: a review of its efficacy as adjuvant therapy and in the treatment of metastatic disease in breast cancer. Drugs Aging 15(5), 389-416 (1999). (Pubitemid 29527873)
145. Sassi G, Striano B, Merlo UA: A reporting system for the assessment of chemotherapy toxicity. J. Oncol. Pharm. Pract. 11(2), 63-67 (2005). (Pubitemid 41131637)
146. Morris RG, Kotasek D, Paltridge G: Disposition of epirubicin and metabolites with repeated courses to cancer patients. Eur. J. Clin. Pharmacol. 40(5), 481-487 (1991).
147. Lunardi G, Venturini M, Vannozzi MO et al.: Influence of alternate sequences of epirubicin and docetaxel on the pharmacokinetic behaviour of both drugs in advanced breast cancer. Ann. Oncol. 13(2), 280-285 (2002). (Pubitemid 34704981)
148. Innocenti F, Iyer L, Ramírez J, Green MD, Ratain MJ: Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7. Drug Metab. Dispos. 29(5), 686-692 (2001). (Pubitemid 32374570)
149. Innocenti F, Liu W, Fackenthal D et al.: Single nucleotide polymorphism discovery and functional assessment of variation in the UDP- glucuronosyltransferase 2B7 gene. Pharmacogenet. Genomics 18(8), 683-697 (2008).
150. Kwara A, Lartey M, Boamah I et al.: Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J. Clin. Pharmacol. 49(9), 1079-1090 (2009).
151. Sawyer MB, Innocenti F, Das S et al.: A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine. Clin. Pharmacol. Ther. 73(6), 566-574 (2003). (Pubitemid 37249128)
152. Holthe M, Rakvåg TN, Klepstad P et al.: Sequence variations in the UDP-glucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients. Pharmacogenomics J. 3(1), 17-26 (2003). (Pubitemid 36432463)
153. Coulbault L, Beaussier M, Verstuyft C et al.: Environmental and genetic factors associated with morphine response in the postoperative period. Clin. Pharmacol. Ther. 79(4), 316-324 (2006).
154. Ross JR, Rutter D, Welsh K et al.: Clinical response to morphine in cancer patients and genetic variation in candidate genes. Pharmacogenomics J. 5(5), 324-336 (2005). (Pubitemid 41486231)
155. Sawyer MB, Damaraju S, Pituskin E et al.: Uridine glucuronosyltransferase 2B7 pharmacogenetics predicts epirubicin clearance and myelosuppression. Presented at: American Society of Clinical Oncology (ASCO) 2009 Annual Meeting. Orlando, FL, USA, 29 May-2 June (2009).
156. Lane AA, Chabner BA: Histone deacetylase inhibitors in cancer therapy. J. Clin. Oncol. 27(32), 5459-5468 (2009).
157. Rasheed W, Bishton M, Johnstone RW, Prince HM: Histone deacetylase inhibitors in lymphoma and solid malignancies. Expert Rev. Anticancer Ther. 8(3), 413-432 (2008). (Pubitemid 351836289)
158. Fakih MG, Pendyala L, Fetterly G et al.: A Phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory colorectal cancer. Clin. Cancer Res. 15(9), 3189-3195 (2009).
159. Fujiwara Y, Yamamoto N, Yamada Y et al.: Phase I and pharmacokinetic study of vorinostat (suberoylanilide hydroxamic acid) in Japanese patients with solid tumors. Cancer Sci. 100(9), 1728-1734 (2009).
160. Munster PH, Marchion D, Thomas S et al.: Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker. Br. J. Cancer 101(7), 1044-1050 (2009).
161. Du L, Musson DG, Wang AQ: High turbulence liquid chromatography online extraction and tandem mass spectrometry for the simultaneous determination of suberoylanilide hydroxamic acid and its two metabolites in human serum. Rapid Commun. Mass Spectrom. 19(13), 1779-1787 (2005). (Pubitemid 40886702)
162. Du L, Musson DG, Wang AQ: Stability studies of vorinostat and its two metabolites in human plasma, serum and urine. J. Pharm. Biomed. Anal. 42(5), 556-564 (2006). (Pubitemid 44636087)
163. Parise RA, Holleran JL, Beumer JH, Ramalingam S, Egorin MJ: A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 840(2), 108-115 (2006). (Pubitemid 44163473)
164. Balliet RM, Chen G, Gallagher CJ, Dellinger RW, Sun D, Lazarus P: Characterization of UGTs active against SAHA and association between SAHA glucuronidation activity phenotype with UGT genotype. Cancer Res. 69(7), 2981-2989 (2009).
165. Kang S, Ramirez J, House L, Ratain MJ: In vitro glucuronidation of vorinostat. Presented at: American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2009 Annual Meeting. National Harbor, MD, USA, 18-21 March (2009).
166. Christian BA, Grever MR, Byrd JC, Lin TS: Flavopiridol in chronic lymphocytic leukemia: a concise review. Clin. Lymphoma Myeloma 9(Suppl. 3), S179-S185 (2009).
167. Innocenti F, Stadler WM, Iyer L, Ramírez J, Vokes EE, Ratain MJ: Flavopiridol metabolism in cancer patients is associated with the occurrence of diarrhea. Clin. Cancer Res. 6(9), 3400-3405 (2000).
168. Thomas J, Tutsch K, Arzoomanian R et al.: Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase (CDK) inhibitor flavopiridol. Presented at: American Society of Clinical Oncology (ASCO) 1998 Annual Meeting. Los Angeles, CA, USA, 16-19 May (1998).
169. Senderowicz AM, Headlee D, Stinson SF et al.: Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J. Clin. Oncol. 16(9), 2986-2999 (1998). (Pubitemid 28417418)
170. Hagenauer B, Salamon A, Thalhammer T et al.: In vitro glucuronidation of the cyclin-dependent kinase inhibitor flavopiridol by rat and human liver microsomes: involvement of UDP-glucuronosyltransferases 1A1 and 1A9. Drug Metab. Dispos. 29(4 Pt 1), 407-414 (2001). (Pubitemid 32275554)
171. Ramírez J, Iyer L, Journault K et al.: In vitro characterization of hepatic flavopiridol metabolism using human liver microsomes and recombinant UGT enzymes. Pharm. Res. 19(5), 588-594 (2002). (Pubitemid 34553664)
172. Zhai S, Sausville EA, Senderowicz AM et al.: Clinical pharmacology and pharmacogenetics of flavopiridol 1-h i.v. infusion in patients with refractory neoplasms. Anticancer Drugs. 14(2), 125-135 (2003). (Pubitemid 36269751)
173. Yoshida M, Kabe Y, Wada T, Asai A, Handa H: A new mechanism of 6-((2-(dimethylamino) ethyl)amino)-3-hydroxy-7H-indeno(2,1-c) quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads. Mol. Pharmacol. 73(3), 987-994 (2008). (Pubitemid 351397903)
174. Iyer L, Mortell MA, Azuma R et al.: Glucuronidation of TAS-103: a novel anticancer agent. Presented at: American Society of Clinical Oncology (ASCO) 1998 Annual Meeting. Los Angeles, CA, USA, 16-19 May (1998).
175. Ewesuedo RB, Iyer L, Das S et al.: Phase I clinical and pharmacogenetic study of weekly TAS-103 in patients with advanced cancer. J. Clin. Oncol. 19(7), 2084-2090 (2001). (Pubitemid 32702554)
176. Lévesque E, Beaulieu M, Green MD et al.: Isolation and characterization of UGT2B15(Y85): a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics 7(4), 317-325 (1997). (Pubitemid 27356932)
177. Court MH, Duan SX, Guillemette C et al.: Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9. Drug Metab. Dispos. 30(11), 1257-1265 (2002). (Pubitemid 35265834)
178. Court MH, Hao Q, Krishnaswamy S et al.: UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J. Pharmacol. Exp. Ther. 310(2), 656-665 (2004). (Pubitemid 38988911)
179. He X, Hesse LM, Hazarika S et al.: Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletion. Br. J. Clin. Pharmacol. 68(5), 721-730 (2009).
180. Chung JY, Cho JY, Yu KS et al.: Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers. Clin. Pharmacol. Ther. 77(6), 486-494 (2005).
181. Ciotti M, Marrone A, Potter C et al.: Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications. Pharmacogenetics 7(6), 485-495 (1997). (Pubitemid 27517577)
182. Nagar S, Zalatoris JJ, Blanchard RL: Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells. Pharmacogenetics 14(8), 487-499 (2004). (Pubitemid 39100001)
183. Krishnaswamy S, Hao Q, Al-Rohaimi A et al.: UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J. Pharmacol. Exp. Ther. 313(3), 1340-1346 (2005). (Pubitemid 40727040)
184. Van Oijen MG, Barthélémy C, Janssen MJ et al.: Effect of genetic polymorphisms in UDP-glucuronosyltransferase 1A6 (UGT1A6) on acetylsalicylic acid metabolism in healthy female volunteers. Pharmacology 83(4), 237-242 (2009).
185. Tankanitlert J, Morales NP, Howard TA et al.: Effects of combined UDP-glucuronosyltransferase (UGT) 1A1*28 and 1A6*2 on paracetamol pharmacokinetics in b-thalassemia/HbE. Pharmacology 79(2), 97-103 (2007). (Pubitemid 46555221)
186. Ehmer U, Vogel A, Schütte JK et al.: Variation of hepatic glucuronidation: novel functional polymorphisms of the UDP- glucuronosyltransferase UGT1A4. Hepatology 39(4), 970-977 (2004). (Pubitemid 38428936)
187. Innocenti F, Mirkov S, Ramírez J et al.: In vitro glucuronidation of ABT-751, a novel anticancer agent. Presented at: American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2004 Annual Meeting. Miami Beach, FL, USA, 24-27 March (2004).
188. Hande KR, Hagey A, Berlin J et al.: The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: results of a Phase 1 study. Clin. Cancer Res. 12(9), 2834-2840 (2006). (Pubitemid 43752124)
189. Rudek MA, Zhao M, He P, Messersmith WA, Baker SD: Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate ABT-751, ABT-751 glucuronide, and ABT-751 sulfate in human plasma for clinical pharmacology studies. J. Pharm. Biomed. Anal. 42(2), 253-260 (2006). (Pubitemid 44279332)
190. Lazarus P, Sun D: Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen and aromatase inhibitors. Drug Metab. Rev. 42(1), 176-188 (2010).
191. Mareck U, Geyer H, Guddat S et al.: Identification of the aromatase inhibitors anastrozole and exemestane in human urine using liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 20(12), 1954-1962 (2006). (Pubitemid 43893351)
192. Kamath AV, Wang J, Lee FY et al.: Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL. Cancer Chemother. Pharmacol. 61(3), 365-376 (2007). (Pubitemid 350275972)
193. Liu H, Bolton JL, Thatcher GR: Chemical modification modulates estrogenic activity, oxidative reactivity, and metabolic stability in 4́F-DMA, a new benzothiophene selective estrogen receptor modulator. Chem. Res. Toxicol. 19(6), 779-787 (2006). (Pubitemid 43939058)
194. Miners JO, Valente L, Lillywhite KJ et al.: Preclinical prediction of factors influencing the elimination of 5,6-dimethylxanthenone-4-acetic acid, a new anticancer drug. Cancer Res. 57(2), 284-289 (1997). (Pubitemid 27036607)
195. Jameson MB, Baguley BC, Kestell P et al.: Cancer Research (UK) Phase I/II Trials Committee: Pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid (AS1404), a novel vascular disrupting agent, in Phase I clinical trial. Cancer Chemother. Pharmacol. 59(5), 681-687 (2007).
196. Zhou SF, Paxton JW, Tingle MD et al.: Identification and reactivity of the major metabolite (b-1-glucuronide) of the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in humans. Xenobiotica 31(5), 277-293 (2001).
197. Zhou S, Kestell P, Baguley BC, Paxton JW: Preclinical factors influencing the relative contributions of Phase I and II enzymes to the metabolism of the experimental anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid. Biochem. Pharmacol. 65(1), 109-120 (2003).
198. Takanashi S, Bachur NR: Adriamycin metabolism in man. Evidence from urinary metabolites. Drug Metab. Dispos. 4(1), 79-87 (1976).
199. Weenen H, Lankelma J, Penders PG et al.: Pharmacokinetics of 4́-epi-doxorubicin in man. Invest New Drugs. 1(1), 59-64 (1983).
200. Weenen H, Van Maanen JM, De Planque MM, McVie JG, Pinedo HM: Metabolism of 4́-modified analogs of doxorubicin. Unique glucuronidation pathway for 4́-epidoxorubicin. Eur. J. Cancer Clin. Oncol. 20(7), 919-926 (1984).
201. Cassinelli G, Configliacchi E, Penco S et al.: Separation, characterization, and analysis of epirubicin (4́-epidoxorubicin) and its metabolites from human urine. Drug Metab. Dispos. 12(4), 506-510 (1984).
202. Robert J, David M, Granger C: Metabolism of epirubicin to glucuronides: relationship to the pharmacodynamics of the drug. Cancer Chemother. Pharmacol. 27(2), 147-150 (1990).
203. Robert J, Vrignaud P, Nguyen-Ngoc T, Iliadis A, Mauriac L, Hurteloup P: Comparative pharmacokinetics and metabolism of doxorubicin and epirubicin in patients with metastatic breast cancer. Cancer Treat. Rep. 69(6), 633-640 (1985).
204. Zaya MJ, Hines RN, Stevens JC: Epirubicin glucuronidation and UGT2B7 developmental expression. Drug Metab. Dispos. 34(12), 2097-2101 (2006).
205. Ling J, Johnson KA, Miao Z et al.: Metabolism and excretion of erlotinib, a small molecule inhibitor of epidermal growth factor receptor tyrosine kinase, in healthy male volunteers. Drug Metab. Dispos. 34(3), 420-426 (2006).
206. Watanabe Y, Nakajima M, Ohashi N, Kume T, Yokoi T: Glucuronidation of etoposide in human liver microsomes is specifically catalyzed by UDP-glucuronosyltransferase 1A1. Drug Metab. Dispos. 31(5), 589-595 (2003).
207. Wen Z, Tallman MN, Ali SY, Smith PC: UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab. Dispos. 35(3), 371-380 (2007).
208. Ito M, Yamamoto K, Maruo Y, Sato H, Fujiyama Y, Bamba T: Effect of a conserved mutation in uridine diphosphate glucuronosyltransferase 1A1 and 1A6 on glucuronidation of a metabolite of flutamide. Eur. J. Clin. Pharmacol. 58(1), 11-14 (2002).
209. Helsby NA, Goldthorpe MA, Tang MH et al.: Influence of mustard group structure on pathways of in vitro metabolism of anticancer N-(2-hydroxyethyl)-3, 5-dinitrobenzamide 2-mustard prodrugs. Drug Metab. Dispos. 36(2), 353-360 (2008).
210. Van sen Bongard HJ, Pluim D et al.: An excretion balance and pharmacokinetic study of the novel anticancer agent E7070 in cancer patients. Anticancer Drugs. 13(8), 807-814 (2002).
211. Beumer JH, Hillebrand MJ, Pluim D et al.: Human metabolism of [(C14)]indisulam following i.v. infusion in cancer patients. Invest. New Drugs 23(4), 317-330 (2005).
212. Prakash C, Johnson KA, Gardner MJ: Disposition of lasofoxifene, a next-generation selective estrogen receptor modulator, in healthy male subjects. Drug Metab. Dispos. 36(7), 1218-1226 (2008).
213. Lakhani NJ, Sparreboom A, Xu X et al.: Characterization of in vitro and in vivo metabolic pathways of the investigational anticancer agent, 2-methoxyestradiol. J. Pharm. Sci. 96(7), 1821-1831 (2007).
214. Cummings J, Ethell BT, Jardine L et al.: Glucuronidation as a mechanism of intrinsic drug resistance in human colon cancer: reversal of resistance by food additives. Cancer Res. 63(23), 8443-8450 (2003).
215. Cummings J, Ethell BT, Jardine L, Burchell B: Glucuronidation of SN-38 and NU/ICRF in human colon cancer and adjacent normal colon. Anticancer Res. 26(3B), 2189-2196 (2006).
216. Cummings J, Boyd G, Ethell BT et al.: Enhanced clearance of topoisomerase I inhibitors from human colon cancer cells by glucuronidation. Biochem. Pharmacol. 63(4), 607-613 (2002).
217. Dalvie D, Kang P, Zientek M, Xiang C, Zhou S, Obach RS: Effect of intestinal glucuronidation in limiting hepatic exposure and bioactivation of raloxifene in humans and rats. Chem. Res. Toxicol. 21(12), 2260-2271 (2008).
218. Kim AR, Lim SJ, Lee BJ: Metabolic inhibition and kinetics of raloxifene by pharmaceutical excipients in human liver microsomes. Int. J. Pharm. 368(1-2), 37-44 (2009).
219. Azuma R, Saeki M, Yamamoto Y, Hagiwara Y, Grochow LB, Donehower RC: Metabolism and urinary excretion of a new quinoline anticancer drug, TAS-103, in humans. Xenobiotica 32(1), 63-72 (2002).
220. Garner RC, Goris I, Laenen AA et al.: Evaluation of accelerator mass spectrometry in a human mass balance and pharmacokinetic study-experience with 14C-labeled (R)-6-[amino(4-chlorophenyl) (1-methyl-1H-imidazol-5-yl)methyl]-4- (3-chlorophenyl)-1-methyl-2(1H)-quinolinone (R115777), a farnesyl transferase inhibitor. Drug Metab. Dispos. 30(7), 823-830 (2002).
221. Zhang S, Zannikos P, Awada A et al.: Pharmacokinetics of tipifamib after oral and intravenous administration in subjects with advanced cancer. J. Clin. Pharmacol. 46(10), 1116-1127 (2006).
222. Rosing H, Van Zomeren DM, Doyle E, Bult A, Beijnen JH: O-glucuronidation, a newly identified metabolic pathway for topotecan and N-desmethyl topotecan. Anticancer Drugs. 9(7), 587-592 (1998).
223. Aono S, Adachi Y, Uyama E et al.: Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome. Lancet 345(8955), 958-959 (1995).
224. Beutler E, Gelbart T, Demina A: Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc. Natl. Acad. Sci. USA. 95(14), 8170-8174 (1998).
225. Sugatani J, Kojima H, Ueda A et al.: The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology 33(5), 1232-1238 (2001).
226. Wiener D, Doerge DR, Fang JL, Upadhyaya P, Lazarus P: Characterization of N-glucuronidation of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol (NNAL) in human liver: importance of UDP-glucuronosyltransferase 1A4. Drug Metab. Dispos. 32(1), 72-79 (2004).
227. Saeki M, Saito Y, Jinno H et al.: Genetic variations and haplotypes of UGT1A4 in a Japanese population. Drug Metab. Pharmacokinet. 20(2), 144-151 (2005).
228. Huang YH, Galijatovic A, Nguyen N et al.: Identification and functional characterization of UDP glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3. Pharmacogenetics 12(4), 287-297 (2002).
229. Bernard O, Guillemette C: The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab. Dispos. 32(8), 775-778 (2004).
230. Thomas SS, Li SS, Lampe JW, Potter JD, Bigler J: Genetic variability, haplotypes, and htSNPs for exons 1 at the human UGT1A locus. Hum. Mutat. 27(7), 717 (2006).
231. Elahi A, Bendaly J, Zheng Z et al.: Detection of UGT1A10 polymorphisms and their association with orolaryngeal carcinoma risk. Cancer 98(4), 872-880 (2003).
232. Jin C, Miners JO, Lillywhite KJ, Mackenzie PI: Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J. Pharmacol. Exp. Ther. 264(1), 475-479 (1993).
233. Coffman BL, King CD, Rios GR, Tephly TR: The glucuronidation of opioids, other xenobiotics, and androgens by human UGT2B7Y(268) and UGT2B7H(268). Drug Metab. Dispos. 26(1), 73-77 (1998).
234. Bhasker CR, McKinnon W, Stone A et al.: Genetic polymorphism of UDP-glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic diversity of alleles and potential clinical significance. Pharmacogenetics 10(8), 679-685 (2000).
235. Wilson W 3rd, Pardo-Manuel de Villena F, Lyn-Cook BD et al.: Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics 84(4), 707-714 (2004).
236. Murata M, Warren EH, Riddell SR: A human minor histocompatibility antigen resulting from differential expression due to a gene deletion. J. Exp. Med. 197(10), 1279-1289 (2003).
237. Lazarus P, Zheng Y, Aaron Runkle E, Muscat JE, Wiener D: Genotype-phenotype correlation between the polymorphic UGT2B17 gene deletion and NNAL glucuronidation activities in human liver microsomes. Pharmacogenet. Genomics 15(11), 769-778 (2005).
238. Jakobsson J, Ekström L, Inotsume N et al.: Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. J. Clin. Endocrinol. Metab. 91(2), 687-693(2006).
239. Gallagher CJ, Muscat JE, Hicks AN et al.: The UDP-glucuronosyltransferase 2B17 gene deletion polymorphism: sex-specific association with urinary 4-(methylnitrosamino)-1-(3pyridyl)-1-butanol glucuronidation phenotype and risk for lung cancer. Cancer Epidemiol. Biomarkers Prev. 16(4), 823-828 (2007).
240. Swanson C, Mellström D, Lorentzon M et al.: The uridine diphosphate glucuronosyltransferase 2B15 D85Y and 2B17 deletion polymorphisms predict the glucuronidation pattern of androgens and fat mass in men. J. Clin. Endocrinol. Metab. 92(12), 4878-4882 (2007).
241. Yang TL, Chen XD, Guo Y et al.: Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis. Am J. Hum Genet. 83(6), 663-674 (2008).
242. Karypidis AH, Olsson M, Andersson SO, Rane A, Ekström L: Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate. Pharmacogenomics J. 8(2), 147-151 (2008).
243. Ménard V, Eap O, Harvey M, Guillemette C, Lévesque E: Copy-number variations (CNVs) of the human sex steroid metabolizing genes UGT2B17 and UGT2B28 and their associations with a UGT2B15 functional polymorphism. Hum. Mutat. 30(9), 1310-1319 (2009).