Skip to main content

Advertisement

SpringerLink
Log in

Individualized chemotherapy based on genetic and genomic profiling

  • Published:
Current Colorectal Cancer Reports

Abstract

The treatment of colorectal cancer has evolved over the past few years to multidrug therapy including 5-fluouracil (5-FU), irinotecan (CPT-11), and oxaliplatin combination regimens. The addition of novel agents such as bevacizumab and cetuximab has added to the efficacy of chemotherapy in this disease. Identification of molecular determinants of 5-FU, irinotecan, and oxaliplatin efficacy and toxicity is of critical importance for the development of more efficient and less toxic treatment strategies for patients with colon cancer. Markers have been identified that may predict response, survival and toxicity to 5-FU, CPT-11, and platinum-based chemotherapy in patients with advanced colorectal cancer. This review explores these markers as well as potential new markers that have been identified for irinotecan and targeted therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. 2005 Cancer Facts and Figures. New York: American Cancer Society; 2005.

  2. Moertel CG: Chemotherapy for colorectal cancer. N Engl J Med 1994, 330:1136–42.

    Article  PubMed  CAS  Google Scholar 

  3. Grem JL: 5-Fluorouracil plus leucovorin in cancer therapy. In Principles and Practice of Oncology Update Series. Edited by De Vita VT Jr HS, Rosenberg SA. Philadelphia: J.B. Lippincott; 1998.

    Google Scholar 

  4. Kundu NG, Heidelberger C: Cyclopenta(f)isoquinoline derivatives designed to bind specifically to native deoxyribonucleic acid. 3. Interaction of 6-carbamylmethyl-8-methyl- 7H-cyclopenta(f)isoquinolin-3(2H)-one with deoxyribonucleic acids and polydeoxyribonucleotides. Biochem Biophys Res Commun 1974, 60:561–568.

    Article  PubMed  CAS  Google Scholar 

  5. Danenberg PV: Thymidylate synthetase - a target enzyme in cancer chemotherapy. Biochim Biophys Acta 1977, 473:73–92.

    PubMed  CAS  Google Scholar 

  6. Berger SH, Jenh CH, Johnson LF, et al.: Thymidylate synthase overproduction and gene amplification in fluorodeoxyuridine- resistant human cells. Mol Pharmacol 1985, 28:461–7.

    PubMed  CAS  Google Scholar 

  7. Danenberg KD, Danenberg PV: Activity of thymidylate synthetase and its inhibition by 5-fluorouracil in highly enzyme-overproducing cells resistant to 10-propargyl-5, 8-dideazafolate. Mol Pharmacol 1989, 36:219–223.

    PubMed  CAS  Google Scholar 

  8. Spears CP, Gustavsson BG, Berne M, et al.: Mechanisms of innate resistance to thymidylate synthase inhibition after 5-fluorouracil. Cancer Res 1988, 48:5894–5900.

    PubMed  CAS  Google Scholar 

  9. Popat S, Matakidou A, Houlston RS: Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol 2004, 22:529–536. This review of TS as a prognostic marker summarizes the current literature.

    Article  PubMed  CAS  Google Scholar 

  10. Aschele C, Debernardis D, Casazza S, et al.: Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy. J Clin Oncol 1999, 17:1760–1770.

    PubMed  CAS  Google Scholar 

  11. Leichman CG, Lenz HJ, Leichman L, et al.: Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol 1997, 15:3223–3229.

    PubMed  CAS  Google Scholar 

  12. Salonga D, Danenberg KD, Johnson M, et al.: Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clin Cancer Res 2000, 6:1322–1327. Low gene expression of TS, TP, and DPD are all independent predictors of 5-FU response. Patients with low gene expression of all three genes had a significantly longer survival compared with patients that had a high value of any one of these genes.

    PubMed  CAS  Google Scholar 

  13. Ichikawa W, Uetake H, Shirota Y, et al.: Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. Clin Cancer Res 2003, 9:786–791.

    PubMed  CAS  Google Scholar 

  14. Yamada Y, Yasui H, Goto A, et al.: Phase I study of irinotecan and S-1 combination therapy in patients with metastatic gastric cancer. Int J Clin Oncol 2003, 8:374–380.

    Article  PubMed  CAS  Google Scholar 

  15. Aschele C, Debernardis D, Tunesi G, et al.: Thymidylate synthase protein expression in primary colorectal cancer compared with the corresponding distant metastases and relationship with the clinical response to 5-fluorouracil. Clin Cancer Res 2000, 6:4797–4802.

    PubMed  CAS  Google Scholar 

  16. Gorlick R, Metzger R, Danenberg KD, et al.: Higher levels of thymidylate synthase gene expression are observed in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma. J Clin Oncol 1998, 16:1465–1469.

    PubMed  CAS  Google Scholar 

  17. Cascinu S, Aschele C, Barni S, et al.: Thymidylate synthase protein expression in advanced colon cancer: correlation with the site of metastasis and the clinical response to leucovorin-modulated bolus 5-fluorouracil. Clin Cancer Res 1999, 5:1996–1999.

    PubMed  CAS  Google Scholar 

  18. Horie N, Aiba H, Oguro K, et al.: Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5’-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct 1995, 20:191–197.

    Article  PubMed  CAS  Google Scholar 

  19. Luo HR, Lu XM, Yao YG, et al.: Length polymorphism of thymidylate synthase regulatory region in Chinese populations and evolution of the novel alleles. Biochem Genet 2002, 40:41–51.

    Article  PubMed  CAS  Google Scholar 

  20. Kawakami K, Salonga D, Park JM, et al.: Different lengths of a polymorphic repeat sequence in the thymidylate synthase gene affect translational efficiency but not its gene expression. Clin Cancer Res 2001, 7:4096–4101.

    PubMed  CAS  Google Scholar 

  21. Marsh S, Collie-Duguid ES, Li T, et al.: Ethnic variation in the thymidylate synthase enhancer region polymorphism among Caucasian and Asian populations. Genomics 1999, 58:310–312.

    Article  PubMed  CAS  Google Scholar 

  22. Kaneda S, Takeishi K, Ayusawa D, et al.: Role in translation of a triple tandemly repeated sequence in the 5’-untranslated region of human thymidylate synthase mRNA. Nucleic Acids Res 1987, 15:1259–1270.

    Article  PubMed  CAS  Google Scholar 

  23. Marsh S, McKay JA, Cassidy J, et al.: Polymorphism in the thymidylate synthase promoter enhancer region in colorectal cancer. Int J Oncol 2001, 19:383–386.

    PubMed  CAS  Google Scholar 

  24. Pullarkat ST, Stoehlmacher J, Ghaderi V, et al.: Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 2001, 1:65–70. In addition to TS protein and RNA expression, gene polymorphisms have been identified that may determine response to therapy. Patients with double tandem repeats have significantly higher response rates to 5-FU. This provides another means of selecting patients.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  26. Lu B, Gil B, Zhang W, et al.: Thymidylate synthase polymorphism predicts pelvic recurrence in rectal cancer patients treated with combined modalities [abstract 2237]. Proc Am Soc Clin Oncol 2002, 21. http://www.asco.org/ac/ 1,1003,_12-002577.asp

  27. Mandola M, Stoehlmacher J, Muller-Weeks S, et al.: A novel single nucleotide polymorphism within the 5’ tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res 2003, 63:2898–2904.

    PubMed  CAS  Google Scholar 

  28. Schaaf M, Cidlowski J: AUUUA motifs in the 3’UTR of human glucocorticoid receptor alpha and beta mRNA destabilize mRNA and decrease receptor protein expression. Steroids 2002, 67:627–636.

    Article  PubMed  CAS  Google Scholar 

  29. Mandola MV, Stoehlmacher J, Zhang W, et al.: A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics 2004, 14:319–327.

    Article  PubMed  CAS  Google Scholar 

  30. Ichikawa W, Uetake H, Shirota Y, et al.: Combination of dihydropyrimidin dehydrogenase and thymidylate synthase gene expression in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. Clin Cancer Res 2003, 9:786–791.

    PubMed  CAS  Google Scholar 

  31. Farrugia D, Ford H, Cunningham D, et al.: Thymidylate synthase expression in advanced colorectal cancer predicts for response to ralitrexed. Clin Cancer Res 2003, 9:792–801.

    PubMed  CAS  Google Scholar 

  32. Shirota Y, Stoehlmacher J, Brabender J, et al.: ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 2001, 19:4298–4304. Potential predictive markers of response to 5-FU/oxaliplatin-based regimens include both TS and ERCC1.

    PubMed  CAS  Google Scholar 

  33. Kubota T, Watanabe M, Otani Y, et al.: Different pathways of 5-fluorouracil metabolism after continuous venous or bolus injection in patients with colon carcinoma: possible predictive value of thymidylate synthase mRNA and ribonucleotide reductase for 5-fluorouracil. Anticancer Res 2002, 22:3537–3540.

    PubMed  CAS  Google Scholar 

  34. McLeod H, Sargent D, Marsh S, et al.: Pharmacogenetic analysis of systemic toxicity and response after 5-fluorouracil (5-FU)/ CPT-11, 5-FU/oxaliplatin (oxal), or CPT-11/oxal therapy for advanced colorectal cancer (CRC): results from an intergroup trial [abstract #1013]. Proc Am Soc Clin Oncol 2003. http://ascio.org/ac/1,1003,_12-002577.asp

  35. Heggie GD, Sommadossi JP, Cross DS, et al.: Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res 1987, 47:2203–2206.

    PubMed  CAS  Google Scholar 

  36. McLeod HL, Collie-Duguid ES, Vreken P, et al.: Nomenclature for human DPYD alleles. Pharmacogenetics 1998, 8:455–459.

    PubMed  CAS  Google Scholar 

  37. Diasio RB, Beavers TL, Carpenter JT: Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J Clin Invest 1988, 81:47–51.

    PubMed  CAS  Google Scholar 

  38. Johnson MR, Hageboutros A, Wang K, et al.: Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res 1999, 5:2006–2011.

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  40. Van Kuilenburg AB, Vreken P, Abeling NG, et al.: Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet 1999, 104:1–9.

    Article  PubMed  Google Scholar 

  41. Van Kuilenburg AB, Vreken P, Beex LV, et al.: Heterozygosity for a point mutation in an invariant splice donor site of dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity. Eur J Cancer 1997, 33:2258–2264.

    Article  PubMed  Google Scholar 

  42. Isshi K, Sakuyama T, Gen T, et al.: Predicting 5-FU sensitivity using human colorectal cancer specimens: comparison of tumor dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activities with in vivo chemosensitivity to 5-FU. Int J Clin Oncol 2002, 7:335–342.

    Article  PubMed  CAS  Google Scholar 

  43. Ichikawa W TT, Nihei Z, Shirota Y, et al.: Polymorphism of orotate phosphoribosyl transferase (OPRT) gene and tymidylate synthase tandem repeat (TSTR) predict adverse events (AE) in colorectal cancer (CRC) patients treated with 5-fluorouracil (FU) plus leucovorin (LV) [abstract #1063]. Proc Am Soc Clin Oncol 2003. http://ascio.org/ac/1,1003,_12-002577.asp

  44. Hsiang YH, Liu LF: Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res 1988, 48:1722–1726.

    PubMed  CAS  Google Scholar 

  45. Irinotecan (CPT-11) Investigator’s Brochure. Pfizer: New York, NY.

  46. Gupta E, Mick R, Ramirez J, et al.: Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients. J Clin Oncol 1997, 15:1502–1510.

    PubMed  CAS  Google Scholar 

  47. Rivory LP, Robert J: Identification and kinetics of a betaglucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan. Cancer Chemother Pharmacol 1995, 36:176–179.

    PubMed  CAS  Google Scholar 

  48. Rivory LP, Haaz MC, Canal P, et al.: Pharmacokinetic interrelationships of irinotecan (CPT-11) and its three major plasma metabolites in patients enrolled in phase I/II trials. Clin Cancer Res 1997, 3:1261–1266.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  50. Khanna R, Morton CL, Danks MK, et al.: Proficient metabolism of irinotecan by a human intestinal carboxylesterase. Cancer Res 2000, 60:4725–4728.

    PubMed  CAS  Google Scholar 

  51. Charasson V, Bellott R, Gorry P, et al.: Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38 [abstract #4668]. Proc Am Assoc Cancer Res 2003, 94.

  52. Rivory LP, Riou JF, Haaz MC, et al.: Identification and properties of a major plasma metabolite of irinotecan (CPT-11) isolated from the plasma of patients. Cancer Res 1996, 56:3689–3694.

    PubMed  CAS  Google Scholar 

  53. Haaz MC, Riche C, Rivory LP, et al.: Biosynthesis of an aminopiperidino metabolite of irinotecan [7-ethyl-10- [4-(1-piperidino)-1-piperidino]carbonyloxycamptothecine] by human hepatic microsomes. Drug Metab Dispos 1998, 26:769–774.

    PubMed  CAS  Google Scholar 

  54. Haaz MC, Rivory L, Riche C, et al.: Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions. Cancer Res 1998, 58:468–472.

    PubMed  CAS  Google Scholar 

  55. Rebbeck TR, Jaffe JM, Walker AH, et al.: Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 1998, 90:1225–1229.

    Article  PubMed  CAS  Google Scholar 

  56. 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 1998, 101:847–854.

    PubMed  CAS  Google Scholar 

  57. 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 1999, 65:576–582.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  60. Monaghan G, Ryan M, Seddon R, et al.: Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 1996, 347:578–581.

    Article  PubMed  CAS  Google Scholar 

  61. Sato H, Adachi Y, Koiwai O: The genetic basis of Gilbert’s syndrome. Lancet 1996, 347:557–558.

    Article  PubMed  CAS  Google Scholar 

  62. Saka H, Ando Y, Sugiura S, et al.: UGT1A1*28 pleomorphism may affect glucuronidation of SN-38 in CPT-11 chemotherapy [abstract #751]. Proc Am Soc Clin Oncol 1998. http://ascio.org/ ac/1,1003,_12-002577.asp

  63. Innocenti F, Iyer L, Ratain MJ: Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan. Drug Metab Dispos 2001, 29:596–600.

    PubMed  CAS  Google Scholar 

  64. Iyer L, Das S, Janisch L, et al.: UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J 2002, 2:43–47.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  66. Yamamoto K, Sato H, Fujiyama Y, et al.: 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 1998, 1406:267–273.

    PubMed  CAS  Google Scholar 

  67. Iyer L, Janisch L, Das S, et al.: UGT1A1 Promoter Genotype Correlates with Pharmacokinetics of Irinotecan (CPT-11) [abstract #690]. Proc Am Soc Clin Oncol 2000, x: http://ascio.org/ac/1,1003,_12-002577.asp

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

    PubMed  CAS  Google Scholar 

  69. Ando M, Kitagawa H, Ando Y, et al.: Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP-Glucuronosyltransferase (UGT) 1A1 gene and irinotecan toxicity in Japanese patients [abstract #496]. Proc Am Soc Clin Oncol 2003. http://ascio.org/ac/1,1003,_12-002577.asp

  70. Gagne J, 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 2002, 62:608–617.

    Article  PubMed  CAS  Google Scholar 

  71. Jinno H, Saeki M, Saito Y, et al.: Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients. J Phamacol Exp Ther 2003, 306:688–693.

    Article  CAS  Google Scholar 

  72. Mathijssen RH, Marsh S, Karlsson MO, et al.: Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin Cancer Res 2003, 9:3246–3253.

    PubMed  CAS  Google Scholar 

  73. Di Rienzo A, Hall D, Iyer L, et al.: Two new alleles in the promoter of the bilirubin UDP-GT gene. Am Soc Clin Pharmacol Therapeut 1998, 63:207.

    Google Scholar 

  74. Lampe JW, Bigler J, Horner NK, et al.: UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics 1999, 9:341–349. Toxicity related to irinotecan-based chemotherapy may be associated with particular polymorphisms that appear to vary in ethnic groups.

    Article  PubMed  CAS  Google Scholar 

  75. Vallböhmer D, Iqbal S, Yang DY, et al.: Molecular determinants of irinotecan efficacy. Journal 2005, in press.

  76. Ling YH, Donato NJ, Perez-Soler R: Sensitivity to topoisomerase I inhibitors and cisplatin is associated with epidermal growth factor receptor expression in human cervical squamous carcinoma ME180 sublines. Cancer Chemother Pharmacol 2001, 47:473–480.

    Article  PubMed  CAS  Google Scholar 

  77. Christen RD, Hom DK, Porter DC, et al.: Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. J Clin Invest 1990, 86:1632–1640.

    Article  PubMed  CAS  Google Scholar 

  78. Bleiberg H, de Gramont A: Oxaliplatin plus 5-fluorouracil: clinical experience in patients with advanced colorectal cancer. Semin Oncol 1998, 25:32–39.

    PubMed  CAS  Google Scholar 

  79. Raymond E, Faivre S, Woynarowski JM, et al.: Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 1998, 25:4–12.

    PubMed  CAS  Google Scholar 

  80. Metzger R, Leichman CG, Danenberg KD, et al.: ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol 1998, 16:309–316.

    PubMed  CAS  Google Scholar 

  81. Park DJ, Stoehlmacher J, Zhang W, et al.: ERCC1 polymorphism is associated with differential ERCC1 mRNA levels [abstract #43]. Proc Am Assoc Cancer Res 2002.

  82. Mannervik B: The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol 1985, 57:357–417.

    Article  PubMed  CAS  Google Scholar 

  83. Boyer TD, Vessey DA, Holcomb C, et al.: Studies of the relationship between the catalytic activity and binding of non-substrate ligands by the glutathione S-transferases. Biochem J 1984, 217:179–185.

    PubMed  CAS  Google Scholar 

  84. Terrier P, Townsend AJ, Coindre JM, et al.: An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. Am J Pathol 1990, 137:845–853.

    PubMed  CAS  Google Scholar 

  85. Moscow JA, Fairchild CR, Madden MJ, et al.: Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res 1989, 49:1422–1428.

    PubMed  CAS  Google Scholar 

  86. Tsuchida S, Sato K: Glutathione transferases and cancer. Crit Rev Biochem Mol Biol 1992, 27:337–384.

    PubMed  CAS  Google Scholar 

  87. Board PG, Webb GC, Coggan M: Isolation of a cDNA clone and localization of the human glutathione S-transferase 3 genes to chromosome bands 11q13 and 12q13-14. Ann Hum Genet 1989, 53(Pt 3):205–213.

    PubMed  CAS  Google Scholar 

  88. Zimniak P, Nanduri B, Pikula S, et al.: Naturally occurring human glutathione S-transferase GSTP1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties. Eur J Biochem 1994, 224:893–899.

    Article  PubMed  CAS  Google Scholar 

  89. Nishimura T, Newkirk K, Sessions RB, et al.: Association between expression of glutathione-associated enzymes and response to platinum-based chemotherapy in head and neck cancer. Chem Biol Interact 1998, 111–112:187–198.

    Article  PubMed  Google Scholar 

  90. Lunn RM, Helzlsouer KJ, Parshad R, et al.: XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 2000, 21:551–555.

    Article  PubMed  CAS  Google Scholar 

  91. Spitz MR, Wu X, Wang Y, et al.: Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001, 61:1354–1357.

    PubMed  CAS  Google Scholar 

  92. Vogel U, Dybdahl M, Frentz G, et al.: DNA repair capacity: inconsistency between effect of over-expression of five NER genes and the correlation to mRNA levels in primary lymphocytes. Mutat Res 2000, 461:197–210.

    PubMed  CAS  Google Scholar 

  93. Vallbohmer D, Zhang W, Gordon M, et al.: Molecular determinants of cetuximab efficacy. J Clin Oncol 2005, 23:3536–3544.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, 90033, Los Angeles, CA, USA

    Heinz-Josef Lenz MD

Authors
  1. Syma Iqbal MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heinz-Josef Lenz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iqbal, S., Lenz, HJ. Individualized chemotherapy based on genetic and genomic profiling. Curr colorectal cancer rep 1, 91–102 (2005). https://doi.org/10.1007/s11888-005-0005-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-005-0005-4

Keywords

Search

Navigation