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Target Discovery and Validation Reviews and Protocols pp 327–340Cite as

Treatment Options and Individualized Medicine

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Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 361))

Abstract

Although several drug targets are identified, current strategies in therapy do not take into account that patients vary in their response to drugs, both with respect to efficacy and toxic side effects. Whereas both clinical and histopathologic predictors of prognosis are established in some diseases, a better understanding of the molecular mechanisms that determine treatment response should play an important role in the development of individualized medicine. Treatment optimization will rely on the ability to adjust treatment algorithms for use in the individual patient based on the identification and validation of the factors that critically determine treatment outcomes, including diagnosis, disease phase and characteristics, organ functions, age, and gender. Although the analysis of a single genetic marker (e.g., CYP polymorphisms) may yield significant information that predicts drug response, the prediction obtained from the analysis of several genetic and epigenetic markers is potentially more powerful in selecting patients for effective therapy, whereas sparing those who would not respond or would suffer undesirable side effects. In this chapter, several relevant examples are presented.

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References

  1. Bell, J. (2004) Predicting disease using genomics. Nature 429, 453–456.

    Article  CAS  PubMed  Google Scholar 

  2. Meyer, U. A. (2004) Pharmacogenetics: five decades of therapeutic lessons from genetic diversity. Nat. Rev. Genet. 5, 669–676.

    Article  CAS  PubMed  Google Scholar 

  3. Lai, E. (2001) Application of SNP technologies in medicine: lessons learned and future challenges. Genome Res. 11, 927–929.

    Article  CAS  PubMed  Google Scholar 

  4. Huang, E., Cheng, S. H., Dressman, H., et al. (2003) Gene expression predictors of breast cancer outcomes. Lancet 361, 1590–1596.

    Article  CAS  PubMed  Google Scholar 

  5. Wilkinson, G. R. (2005) Drug metabolism and variability among patients in drug response N. Engl. J. Med. 352, 2211–2221.

    Article  CAS  PubMed  Google Scholar 

  6. Williams, R. S. and Goldschmidt-Clermont, P. J. (2004) The genetics of cardiovascular disease: from genotype to phenotype. Dialogues in Cardiovasc. Med. 9, 3–19.

    Google Scholar 

  7. Dixon, K. and Kopras, E. (2004) Genetic alterations and DNA repair in human carcinogenesis. Semin in Cancer Biol. 14, 441–448.

    Article  CAS  Google Scholar 

  8. Liotta, L. A. and Kohn, E. C. (2001) The microenvironment of the tumour-host interface. Nature 411, 375–379.

    Article  CAS  PubMed  Google Scholar 

  9. Staudt, L. M. (2002) Gene expression profiling of lymphoid malignancies. Annu. Rev. Med. 53, 303–318.

    Article  CAS  PubMed  Google Scholar 

  10. Ingelman-Sundberg, M. (2005) The human genome project and novel aspects of cytochrome P450 research. Toxicol Appl Pharmacol 207, 52–56.

    Article  PubMed  Google Scholar 

  11. Gajecka, M., Rydzanicz, M., Jaskula-Sztul, R., Kujawski, M., Szyfter, W., and Szyfter, K. (2005) CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma. Mut. Res. 574, 112–123.

    CAS  Google Scholar 

  12. Raimondi, S., Boffetta, P., Anttila, S., et al. (2005) Metabolic gene polymorphisms and lung cancer risk in non-smokers. An update of the GSEC study. Mut. Res. 592, 45–47.

    CAS  Google Scholar 

  13. Efferth, T. and Volm, M. (2005) Gluthatione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. In Vivo 19, 225–232.

    CAS  PubMed  Google Scholar 

  14. Anderer, G., Schrappe, M., Brechlin, A. M., et al. (2000) Polymorphisms within glutathione S-transferase genes and initial response to glucocorticoids in childhood acute lymphoblastic leukaemia. Pharmacogenetics 10, 715–726.

    Article  CAS  PubMed  Google Scholar 

  15. Efferth, T. and Volm, M. (2005) Pharmacogenetics for individualized cancer chemotherapy. Pharmacology Therapeutics 107, 155–176.

    Article  CAS  PubMed  Google Scholar 

  16. Toffoli, G., Cecchin, E., Corona, G., and Boiocchi, M. (2003) Pharmacogenetics of irinotecan. Curr. Med. Chem. Anti-Canc. Agents 3, 225–237.

    Article  CAS  Google Scholar 

  17. Yamayoshi, Y., Iida, E., and Tanigawara, Y. (2005) Cancer pharmacogenomics: international trends. Int. J. Clin. Oncol. 10, 5–13.

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  19. Costea, I., Moghrabi, A., and Krajinovic, M. (2003) The influence of cyclin D1 (CCND1) 870A>G polymorphism and CCND1-thymidylate synthase (TS) genegene interaction on the outcome of childhood acute lymphoblastic leukaemia. Pharmacogenetics 13, 577–580.

    Article  CAS  PubMed  Google Scholar 

  20. Lynch, T. J., Bell, D. W., Sordella, R., et al. (2004) Activating mutations in the Epidermal Gorowth Factor Receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139.

    Article  CAS  PubMed  Google Scholar 

  21. Piccart, M. J., Di Leo, A., and Hamilton, A. (2000) HER2: a predictive factor ready to use in the daily management of breast cancer patient? Eur. J. Cancer 36, 1755–1761.

    Article  CAS  PubMed  Google Scholar 

  22. Duffy, M. J. (2002) Urokinase plasminogen activator and its inhibitor, PAI-1, as prognostic marlers in breast cancer: from pilot to level 1 evidence studies. Clin. Chem. 48, 1194–1197.

    CAS  PubMed  Google Scholar 

  23. Andreasen, P. A., Kjoller, L., Christensen, L., and Duffy, M. J. (1997) The urokinase-type plasminogen activator in cancer metastasis: a review. Int. J. Cancer 72, 1–22.

    Article  CAS  PubMed  Google Scholar 

  24. Efferth, T. (2001) The human ATP-binding cassette transporter genes: from the bench to the bedside. Curr. Mol. Med. 1, 45–65.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Lesko, L. J. and Woodcock, J. (2004) Translation of pharmacogenomics and pharmacogenetics: a regulatory perspective. Nat. Rev. Drug Discov. 3, 763–769.

    Article  CAS  PubMed  Google Scholar 

  27. Margalit, O., Somech, R., Amariglio, N., and Rechavi, G. (2005) Microarray-based gene expression profiling of hematologic malignancies: basic concepts and clinical applications. Blood Rev. 19, 223–234.

    Article  CAS  PubMed  Google Scholar 

  28. Sorlie, T., Perou, C. M., Tibshirani, R., et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. USA 98, 10,869–10,874.

    Article  CAS  PubMed  Google Scholar 

  29. Stock, M. and Otto, F. (2005) Gene deregulation in gastric cancer. Gene 360, 1–19.

    Article  CAS  PubMed  Google Scholar 

  30. Terra, S. G., Hamilton, K. K., Pauly, D. F., et al. (2005) β1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to β-blocker therapy. Pharmacogen. Genom. 15, 227–234.

    Article  CAS  Google Scholar 

  31. Kaye, D. M., Smirk, B., Williams, C., Jennings, G., Esler, M., and Holst, D. (2003) β-Adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogen. 13, 379–382.

    Article  CAS  Google Scholar 

  32. Rigat, B., Hubert, C., Alhenc-Gelas, F., Cambien, F., Corvol, P., and Soubrier, F. (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J. Clin. Invest. 86, 1343–1346.

    Article  CAS  PubMed  Google Scholar 

  33. Ihnken, R., Verho, K., Gross, M., and Marz, W. (1996) Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with increased plasma angiotensin-converting enzyme activity but not with increased risk for myocardial infarction and coronary artery disease. Ann. Intern. Med. 125, 19–25.

    PubMed  Google Scholar 

  34. Andersson, B. and Sylven, C. (1996) The DD genotype of the angiotensin-converting enzyme gene is associated with increased mortality in idiopathic heart failure. J. Am. Coll. Cardiol. 28, 162–167.

    Article  CAS  PubMed  Google Scholar 

  35. McNamara, D. M., Holubkov, R., Postava, L., et al. (2004) Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure. J. Am. Coll. Cardiol. 44, 2019–2026.

    Article  CAS  PubMed  Google Scholar 

  36. Spiering, W., Kroon, A. A., Fuss-Lejeune, M. J. M. J., and Leeuw, P. W. (2005) Genetic contribution to the acute effects of angiotensin II type 1 receptor blockade. J. Hypertens. 23, 753–758.

    Article  CAS  PubMed  Google Scholar 

  37. Nürnberger, J., Dammer, S., Mitchell, A., et al. (2003) Effect of the C825T polymorphism of the G protein β3 subunit on the systolic blood pressure-lowering effect of clonidine in young, healthy male subjects. Clin. Pharmacol. Ther. 74, 53–60.

    Article  PubMed  Google Scholar 

  38. Mitchell, A., Buhrmann, S., Seifert, A., et al. (2003) Venous response to nitroglycerin is enhanced in young, healthy carriers of the 825T allele of the G protein beta3 subunit gene (GNB3). Clin. Pharmacol. Ther. 74, 499–504.

    Article  CAS  PubMed  Google Scholar 

  39. Rozalski, M., Boncler, M., Luzak, B., and Watala, C. (2005) Genetic factors underlying differential blood platelet sensitivity to inhibitors. Pharmacol Reports 57, 1–13.

    CAS  Google Scholar 

  40. Schmitz, G. and Drobnik, W. (2003) Pharmacogenomics and pharmacogenetics of cholesterol-lowering therapy. Clin. Chem. Lab Med. 41, 581–589.

    Article  CAS  PubMed  Google Scholar 

  41. Higashi, M. K., Veenstra, D. L., Kondo, L. M., et al. (2002) Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 287, 1690–1698.

    Article  CAS  PubMed  Google Scholar 

  42. Rieder, M. J., Reiner, A. P., Gage, B. F., et al. (2005) Effect of VKORC1 Haplotypes on transcriptional regulation and warfarin dose. N. Engl. J. Med. 352, 2285–2293.

    Article  CAS  PubMed  Google Scholar 

  43. Sconce, E. A., Khan, T. I., Wynne, H. A., et al. (2005) The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 106, 2329–2333.

    Article  CAS  PubMed  Google Scholar 

  44. Israel, E., Drazen, J. M., Liggett, S. B., et al. (2000). The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am. J. Respir. Crit. Care Med. 162, 75–80.

    CAS  PubMed  Google Scholar 

  45. Taylor, D. R., Drazen, J. M., Herbison, G. P., et al. (2000) Asthma exacerbations during long term beta agonist use: influence of beta(2) adrenoceptor polymorphism. Thorax 55, 762–767.

    Article  CAS  PubMed  Google Scholar 

  46. Israel, E., Chinchilli, V. M., Ford, J. G., et al. (2004) Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 364, 1505–1512.

    Article  CAS  PubMed  Google Scholar 

  47. Drysdale, C. M., McGraw, D. W., Stack, C. B., et al. (2000) Complex promoter and coding region β2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc. Acad. Natl. Sci. USA 97, 10,483–10,488.

    Article  CAS  Google Scholar 

  48. Tantisira, K. G., Small, K. M., Litonjua, A. A., Weiss, S. T., and Liggett, S. B. (2005) Molecular properties and pharmacogenetics of a polymorphism of adenylyl cyclase type 9 in asthma: interaction between β-agonist and corticosteroid pathways. Hum. Mol. Gen. 14, 1671–1677.

    Article  CAS  PubMed  Google Scholar 

  49. Drazen, J. M., Yandava, C. N., Dube, L., et al. (1999) Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat. Genet. 22, 168–170.

    Article  CAS  PubMed  Google Scholar 

  50. Ioannidis, J. P. A., Rosenberg, P. S., Goedert, J. J., et al. (2001) Effects of CCR5-32, CCR2-64I, and SDF-1 3′A alleles on HIV-1 disease progression: an international metaanalysis of individual-patient data. Ann. Intern. Med. 135, 782–795.

    CAS  PubMed  Google Scholar 

  51. Passam, A., Zafiropoulos, A., Miyakis, S., et al. (2005) CCR2-64I and CXCL123′A alleles confer a favorable prognosis to AIDS patients undergoing HAART therapy. J. Clin. Virol. 34, 302–309.

    Article  CAS  PubMed  Google Scholar 

  52. Sarrazin, C., Berg, T., Weich, V., et al. (2005) GNB3 C825T polymorphism and response to interferon-alfa/ribavirin treatment in patients with hepatitis C virus genotype 1 (HCV-1) infection. J. Hepatol. 43, 388–393.

    Article  CAS  PubMed  Google Scholar 

  53. Lindemann, M., Barsegian, V., Siffert, W., et al. (2002) Role of G protein beta3 subunit 825T and HLA class II polymorphisms in the immune response after HBV vaccination. Virology 297, 245–252.

    Article  CAS  PubMed  Google Scholar 

  54. Hauge Opdal, S., Melien, Ø., Rootwelt, H., Vege, Å., Arnestad, M., and Rognum, T. O. (2006) The G protein β3 subunit 825C allele is associated with sudden infant death due to infection, teta paediatre, in presst.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway

    Mouldy Sioud

  2. Clinical Research Unit, Section of Clinical Pharmacology, Rikshospitalet University Hospital, Oslo, Norway

    Øyvind Melien

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  1. Mouldy Sioud
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  2. Øyvind Melien
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Editors and Affiliations

  1. Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway

    Mouldy Sioud

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© 2007 Humana Press Inc.

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Sioud, M., Melien, Ø. (2007). Treatment Options and Individualized Medicine. In: Sioud, M. (eds) Target Discovery and Validation Reviews and Protocols. Methods in Molecular Biology™, vol 361. Humana Press. https://doi.org/10.1385/1-59745-208-4:327

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  • DOI: https://doi.org/10.1385/1-59745-208-4:327

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-890-4

  • Online ISBN: 978-1-59745-208-3

  • eBook Packages: Springer Protocols

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