Pharmacogenomics and Nanotechnology Toward Advancing Personalized Medicine

  • Ioannis S. Vizirianakis
  • Elsa P. Amanatiadou
Part of the NanoScience and Technology book series (NANO)


The target of personalized medicine to achieve major benefits for all patients in terms of diagnosis and drug delivery can be facilitated by creating a sincere multidisciplinary information-based infrastructure in health care. To this end, nanotechnology, pharmacogenomics, and informatics can advance the utility of personalized medicine, enable clinical translation of genomic knowledge, empower healthcare environment, and finally improve clinical outcomes.


Adverse Drug Reaction Personalized Medicine Cholinesterase Inhibitor Healthcare Practitioner CYP2D6 Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    I.S. Vizirianakis, Clinical translation of genotyping and haplotyping data: implementation of in vivo pharmacology experience leading drug prescription to pharmacotyping. Clin. Pharmacokinet. 46, 807–824 (2007)CrossRefGoogle Scholar
  2. 2.
    G.S. Ginsburg, H.F. Willard, Genomic and personalized medicine: foundations and applications. Transl. Res. 154, 277–287 (2009)CrossRefGoogle Scholar
  3. 3.
    M. Pirmohamed, B.K. Park, Genetic susceptibility to adverse drug reactions. Trends Pharmacol. Sci. 22, 298–305 (2001)CrossRefGoogle Scholar
  4. 4.
    I.S. Vizirianakis, Improving pharmacotherapy outcomes by pharmacogenomics: from expectation to reality? Pharmacogenomics 6, 701–711 (2005)CrossRefGoogle Scholar
  5. 5.
    K. Braeckmans, S.C. De Smedt, M. Leblans, R. Pauwels, J. Demeester, Encoding microcarriers: present and future technologies. Nat. Rev. Drug Discov. 1, 447–456 (2002)CrossRefGoogle Scholar
  6. 6.
    I.S. Vizirianakis, Nanomedicine and personalized medicine toward the application of pharmacotyping in clinical practice to improve drug delivery outcomes. Nanomedicine 7, 11–17 (2011)CrossRefGoogle Scholar
  7. 7.
    A.D. Roses, Pharmacogenetics and the practice of medicine. Nature 405, 857–865 (2000)CrossRefGoogle Scholar
  8. 8.
    R. Weinshilboum, Inheritance and drug response. N. Engl. J. Med. 348, 529–537 (2003)CrossRefGoogle Scholar
  9. 9.
    W.E. Evans, H.L. McLeod. Pharmacogenomics, drug disposition, drug targets, and side effects. N. Engl. J. Med. 348, 538–549 (2003)CrossRefGoogle Scholar
  10. 10.
    I.S. Vizirianakis, Challenges in current drug delivery from the potential application of pharmacogenomics and personalized medicine in clinical practice. Curr. Drug Deliv. 1, 73–80 (2004)CrossRefGoogle Scholar
  11. 11.
    I.S. Vizirianakis, From defining bioinformatics and pharmacogenomics to developing information-based medicine and pharmacotyping in healthcare, in Handbook of Pharmaceutical Biotechnology, ed. by S.C. Gad (Wiley, New York, 2007), pp. 201–228Google Scholar
  12. 12.
    P. Debbage, Targeted drugs and nanomedicine: present and future. Curr. Pharm. Des. 5, 153–172 (2009)CrossRefGoogle Scholar
  13. 13.
    C. Huttenhower, O. Hofmann, A quick guide to large-scale genomic data mining. PLoS Comput Biol. 6, e1000779 (2010)CrossRefGoogle Scholar
  14. 14.
    I.S. Vizirianakis, Chatzopoulou M., I.D. Bonovolias, I. Nicolaou, V.J. Demopoulos, A.S. Tsiftsoglou, Toward the development of innovative bi-functional agents to induce differentiation and promote apoptosis in leukemia: clinical candidates and perspectives. J. Med. Chem. 53, 6779–6810 (2010)Google Scholar
  15. 15.
    K. Ahn, J. Luo, A. Berg, D. Keefe, R. Wu, Functional mapping of drug response with pharmacodynamic-pharmacokinetic principles. Trends Pharmacol. Sci. 31, 306–311 (2010)CrossRefGoogle Scholar
  16. 16.
    T. Lammers, F. Kiessling, W.E. Hennink, G. Storm, Nanotheranostics and image-guided drug delivery: current concepts and future directions. Mol. Pharm. 7, 1899–1912 (2010)CrossRefGoogle Scholar
  17. 17.
    D.B. Goldstein, S.K. Tate, S.M. Sisodiya, Pharmacogenetics goes genomic. Nat. Rev. Genet. 4, 937–947 (2003)Google Scholar
  18. 18.
    A. Loktionov, Common gene polymorphisms, cancer progression and prognosis. Cancer Lett. 208, 1–33 (2004)CrossRefGoogle Scholar
  19. 19.
    J.L. Anderson, J.F. Carlquist, B.D. Horne, J.B. Muhlestein, Cardiovascular pharmacogenomics: current status, future prospects. J. Cardiovasc. Pharmacol. Ther. 8, 71–83 (2003)CrossRefGoogle Scholar
  20. 20.
    R. Cacabelos, The application of functional genomics to Alzheimer’s disease. Pharmacogenomics 4, 597–621 (2004)CrossRefGoogle Scholar
  21. 21.
    C.M. Ulrich, K. Robien, H.L. Mcleod, Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nat. Rev. Cancer. 3, 912–920 (2003)CrossRefGoogle Scholar
  22. 22.
    I. Sayers, I.P. Hall, Pharmacogenetic approaches in the treatment of asthma. Curr. Allergy Asthma Rep. 5, 101–108 (2005)CrossRefGoogle Scholar
  23. 23.
    G. Müller, Personalized prognosis and diagnosis of type 2 diabetes: vision or fiction? Pharmacology 85, 168–187 (2010)CrossRefGoogle Scholar
  24. 24.
    J.M. Rusnak, R.M. Kisabeth, D.P. Herbert, D.M. McNeil, Pharmacogenomics: a clinician’s primer on emerging technologies for improved patient care. Mayo Clin. Proc. 76, 299–309 (2001)CrossRefGoogle Scholar
  25. 25.
    J.J. McCarthy, R. Hilfiker, The use of single-nucleotide polymorphism in pharmacogenomics. Nat. Biotechnol. 18, 505–508 (2000)CrossRefGoogle Scholar
  26. 26.
    A.E. Carpenter, D.M. Sabatini, Systematic genome-wide screens of gene function. Nat. Rev. Genet. 5, 11–22 (2004)CrossRefGoogle Scholar
  27. 27.
    S.D. Caruthers, S.A. Wickline, G.M. Lanza, Nanotechnological applications in medicine. Curr. Opin. Biotechnol. 18, 26–30 (2007)CrossRefGoogle Scholar
  28. 28.
    M.E. Davis, Z.G. Chen, D.M. Shin, Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7, 771–782 (2008)CrossRefGoogle Scholar
  29. 29.
    K.K. Jain, Innovative diagnostic technologies and their significance for personalized medicine. Mol. Diagn. Ther. 14, 141–147 (2010)Google Scholar
  30. 30.
    M. Ingelman-Sundberg, Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol. Sci. 25, 193–200 (2004)CrossRefGoogle Scholar
  31. 31.
    K.A. Phillips, D.L. Veenstra, E. Oren, J.K. Lee, W. Sadee, Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. J. Am. Med. Assoc. 286, 2270–2279 (2001)CrossRefGoogle Scholar
  32. 32.
    C. Gabelli, Rivastigmine: an update on therapeutic efficacy in Alzheimer’s disease and other conditions. Curr. Med. Res. Opin. 19, 69–82 (2003)Google Scholar
  33. 33.
    D. Bentue-Ferrer, O. Tribut, E. Polard, H. Allain, Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists. CNS Drugs 17, 947–963 (2003)CrossRefGoogle Scholar
  34. 34.
    N.L. Henry, V. Stearns, D.A. Flockhart, D.F. Hayes, M. Riba, Drug interactions and pharmacogenomics in the treatment of breast cancer and depression. Am. J. Psychiatry 165, 1251–1255 (2008)CrossRefGoogle Scholar
  35. 35.
    J.M. Hoskins, L.A. Carey, H.L. McLeod, CYP2D6 and tamoxifen: DNA matters in breast cancer. Nat. Rev. Cancer 9, 576–586 (2009)CrossRefGoogle Scholar
  36. 36.
    C.M. Kelly, D.N. Juurlink, T. Gomes, M. Duong-Hua, K.I. Pritchard, P.C. Austin, L.F. Paszat, Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. Br. Med. J. 340, c693 (2010)CrossRefGoogle Scholar
  37. 37.
    K. Sideras, J.N. Ingle, M.M. Ames, C.L. Loprinzi, D.P. Mrazek, J.L. Black, R.M. Weinshilboum, J.R. Hawse, T.C. Spelsberg, M.P. Goetz, Corescription of tamoxifen and medications that inhibit CYP2D6. J. Clin. Oncol. 28, 2768–2776 (2010)CrossRefGoogle Scholar
  38. 38.
    T.L. Lash, C.L. Rosenberg, Evidence and practice regarding the role for CYP2D6 inhibition in decisions about tamoxifen therapy. J. Clin. Oncol. 28, 1273–1275 (2010)CrossRefGoogle Scholar
  39. 39.
    G.E. Marchant, Small is beautiful: what can nanotechnology do for personalized medicine? Curr. Pharmacogenomics Personalized Med. 7, 231–237 (2009)Google Scholar
  40. 40.
    S. Ekins, Predicting undesirable drug interactions with promiscuous proteins in silico. Drug Discov. Today 9, 276–285 (2004)CrossRefGoogle Scholar
  41. 41.
    S.P. Gardner, Ontologies and semantic data integration. Drug Discov. Today 10, 1001–1007 (2005)CrossRefGoogle Scholar
  42. 42.
    I.S. Vizirianakis, The transformation of pharmacogenetics into pharmacogenomics reinforces personalized medicine towards pharmacotyping for improved patient care, in New Research on Pharmacogenetics, ed. by L.P. Barnes (Nova Science Publishers, Inc, New York, 2007), pp. 1–38Google Scholar
  43. 43.
    G. Schmitz, C. Aslanidis, K.J. Lackner, Pharmacogenomics: implications for laboratory medicine. Clin. Chim. Acta 308, 43–53 (2001)CrossRefGoogle Scholar
  44. 44.
    D.B. Goldstein, Pharmacogenetics in the laboratory and the clinic. N. Engl. J. Med. 348, 553–556 (2003)CrossRefGoogle Scholar
  45. 45.
    A.M. Issa, Ethical perspectives on pharmacogenomic profiling in the drug development process. Nat. Rev. Drug Discov. 1, 300–308 (2002)CrossRefGoogle Scholar
  46. 46.
    W.W. Weber, M.D. Caldwell, J.H. Kurth, Edging toward personalized medicine. Curr. Pharmacogenomics 1, 193–202 (2003)Google Scholar
  47. 47.
    C. Debouck, P.N. Goodfellow, DNA microarrays in drug discovery and development. Nat. Genet. 21(Suppl.), 48–50 (1999)Google Scholar
  48. 48.
    I.S. Vizirianakis, Pharmaceutical education in the wake of genomic technologies for drug development and personalized medicine. Eur. J. Pharm. Sci. 15, 243–250 (2002)CrossRefGoogle Scholar
  49. 49.
    British Pharmacological Society and the Physiological Society. Tackling the need to teach integrative pharmacology and physiology: problems and ways forward. Trends Pharmacol. Sci. 27, 130–133 (2006)Google Scholar
  50. 50.
    P.K. Manasco, P. Rieser, G. Renegar, M. Mosteller, Pharmacogenetics and the genetic basis of ADRs, in Pharmacovigilance, ed. by R.D. Mann, E.B. Andrews (West Sussex, Wiley, 2002), pp. 516–553Google Scholar
  51. 51.
    P. Farahani, M. Levine, Pharmacovigilance in a genomic era. Pharmacogenomics J. 6, 158–161 (2006)CrossRefGoogle Scholar
  52. 52.
    B.M. Psaty, S.P. Burke, Protecting the health of the public-Institute of Medicine recommendations on drug safety. N. Engl. J. Med. 355, 1753–1755 (2006)CrossRefGoogle Scholar
  53. 53.
    P.T. Fitzgerald, M.J. Ackerman, Drug-induced torsades de pointes: the evolving role of pharmacogenetics. Heart Rhythm 2, S30–S37 (2005)CrossRefGoogle Scholar
  54. 54.
    L. Belardinelli, C. Antzelevitch, M.A. Vos, Assessing predictors of drug-induced torsade de pointes. Trends Pharmacol. Sci. 24, 619–625 (2003)CrossRefGoogle Scholar
  55. 55.
    C.C. Liew, V.J. Dzau, Molecular genetics and genomics of heart failure. Nat. Rev. Genet. 5, 811–825 (2004)CrossRefGoogle Scholar
  56. 56.
    W.S. Redfern, L. Carlsson, A.S. Davis, et al., Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc. Res. 58, 32–45 (2003)CrossRefGoogle Scholar
  57. 57.
    R. Roberts, R. Brugada, Genetics and arrhythmias. Annu. Rev. Med. 54, 257–267 (2003)Google Scholar
  58. 58.
    A.M. Aronov, Predictive in silico modeling for hERG channel blockers. Drug Discov. Today 10, 149–155 (2005)CrossRefGoogle Scholar
  59. 59.
    C. Napolitano, S.G. Priori, P.J. Schwartz, et al., Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. J. Am. Med. Assoc. 294, 2975–2980 (2005)CrossRefGoogle Scholar
  60. 60.
    B. Darpo, T. Nebout, P.T. Sager, Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline. J. Clin. Pharmacol. 46, 498–507 (2006)CrossRefGoogle Scholar
  61. 61.
    R.R. Shah, Drugs, QTc interval prolongation and final ICH E14 guideline: an important milestone with challenges ahead. Drug Saf. 28, 1009–1028 (2005)CrossRefGoogle Scholar
  62. 62.
    J.C. Hancox, M.J. McPate, A. El Harchi, Y.H. Zhang, The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol. Ther. 119, 118–132 (2008)CrossRefGoogle Scholar
  63. 63.
    N. Lee, S. Authier, M.K. Pugsley, M.J. Curtis, The continuing evolution of torsades de pointes liability testing methods: is there an end in sight? Toxicol. Appl. Pharmacol. 243, 146–153 (2010)CrossRefGoogle Scholar
  64. 64.
    H.J. Witchel, Drug-induced hERG block and long QT syndrome. Cardiovasc. Ther. 29, 251–259 (2011)CrossRefGoogle Scholar
  65. 65.
    I. Staudacher, P.A. Schweizer, H.A. Katus, D. Thomas, hERG: protein trafficking and potential for therapy and drug side effects. Curr. Opin. Drug. Discov. Devel. 13, 23–30 (2010)Google Scholar
  66. 66.
    E. Halapi, H. Hakonarson, Advances in the development of genetic markers for the diagnosis of disease and drug response. Expert Rev. Mol. Diagn. 2, 411–421 (2002)CrossRefGoogle Scholar
  67. 67.
    J.A. Johnson, W.E. Evans, Molecular diagnostics as a predictive tool: genetics of drug efficacy and toxicity. Trends Mol. Med. 8, 300–305 (2002)CrossRefGoogle Scholar
  68. 68.
    E. Dequeker, S. Ramsden, W.W. Grody, T.T. Stenzel, D.E. Barton, Quality control in molecular genetic testing. Nat. Rev. Genet. 2, 717–723 (2001)CrossRefGoogle Scholar
  69. 69.
    D.A. Lewin, M.P. Weiner, Molecular biomarkers in drug development. Drug Discov. Today 9, 976–983 (2004)CrossRefGoogle Scholar
  70. 70.
    A.G. Hall, S.A. Coulthard, J.A. Irving, Molecular diagnostics: a healthcare perspective. Expert Rev. Mol. Diagn. 3, 13–16 (2003)CrossRefGoogle Scholar
  71. 71.
    B.B. Spear, M. Heath-Chiozzi, J. Huff, Clinical application of pharmacogenetics. Trends Mol. Med. 7, 201–204 (2001)CrossRefGoogle Scholar
  72. 72.
    K. Sangkuhl, D.S. Berlin, R.B. Altman, T.E. Klein, PharmGKB: understanding the effects of individual genetic variants. Drug Metab. Rev. 40, 539–551 (2008)CrossRefGoogle Scholar
  73. 73.
    D. Gurwitz, A. Weizman, M. Rehavi, Education: teaching pharmacogenomics to prepare future physicians and researchers for personalized medicine. Trends Pharmacol. Sci. 24, 122–125 (2003)CrossRefGoogle Scholar
  74. 74.
    M.E. Van den Akker-van Marle, D. Gurwitz, S.B. Detmar, C.M. Enzing, M.M. Hopkins, E. Gutierrez de Mesa, D. Ibarreta, Cost-effectiveness of pharmacogenomics in clinical practice: a case study of thiopurine methyltransferase genotyping in acute lymphoblastic leukemia in Europe. Pharmacogenomics 7, 783–792 (2006)CrossRefGoogle Scholar
  75. 75.
    D. Gurwitz, C. Rodríguez-Antona, K. Payne, W. Newman, J.P. Gisbert, E.G. de Mesa, D. Ibarreta, Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain. Eur. J. Hum. Genet. 17, 991–998 (2009)CrossRefGoogle Scholar
  76. 76.
    N. Fleeman, C. McLeod, A. Bagust, S. Beale, A. Boland, Y. Dundar, A. Jorgensen, et al., The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation. Health Technol. Assess. 14, 1–157 (2010)Google Scholar
  77. 77.
    R.A. McKinnon, M.B. Ward, M.J.A. Sorich, Critical analysis of barriers to the clinical implementation of pharmacogenomics. Ther. Clin. Risk Manag. 3, 751–759 (2007)Google Scholar
  78. 78.
    A.H.B. Wu, N. Babic, K.T.J. Yeo, Implementation of pharmacogenomics into the clinical practice of therapeutics: issues for the clinician and the laboratorian. Personalized Med. 6, 315–327 (2009)CrossRefGoogle Scholar
  79. 79.
    C.R. Flowers, D. Veenstra, The role of cost-effectiveness analysis in the era of pharmacogenomics. Pharmacoeconomics 22, 481–493 (2004)CrossRefGoogle Scholar
  80. 80.
    K. Payne, F.H. Shabaruddin, Cost-effectiveness analysis in pharmacogenomics. Pharmacogenomics 11, 643–646 (2010)Google Scholar
  81. 81.
    W.B. Wong, J.J. Carlson, R. Thariani, D.L. Veenstra, Cost effectiveness of pharmacogenomics: a critical and systematic review. Pharmacoeconomics 28, 1001–1013 (2010)CrossRefGoogle Scholar
  82. 82.
    P. Martin, W.E. Haefeli, M.A. Martin-Facklam, Drug database model as a central element for computer-supported dose adjustment within a CPOE system. J. Am. Med. Inform. Assoc. 11, 427–432 (2004)CrossRefGoogle Scholar
  83. 83.
    S. Orphanoudakis, HYGEIAnet: the integrated regional health information network of Crete. Stud. Health Technol. Inform. 100, 66–78 (2004)Google Scholar
  84. 84.
    M. Mäkinen, J. Forsström, M. Äärimaa, et al., A European survey on the possibilities and obstacles of electronic prescriptions in cross-border healthcare. Telemed. J. E-Health 12, 484–489 (2006)CrossRefGoogle Scholar
  85. 85.
    M.A. Keller, E.S. Gordon, C.B. Stack, N. Gharani, C.J. Sill, T.J. Schmidlen, et al., Coriell Personalized Medicine Collaborative: a prospective study of the utility of personalized medicine. Personalized Med. 7, 310–317 (2010)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ioannis S. Vizirianakis
    • 1
  • Elsa P. Amanatiadou
    • 1
  1. 1.Laboratory of Pharmacology, Department of Pharmaceutical SciencesAristotle University of ThessalonikiThessalonikiGreece

Personalised recommendations