Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC22910.15690/vramn.v67i12.474EDITORIALОТ РЕДАКЦИИPERSONALIZED MEDICINE: STATE-OF-THE-ART AND PROSPECTSПЕРСОНАЛИЗИРОВАННАЯ МЕДИЦИНА: СОВРЕМЕННОЕ СОСТОЯНИЕ И ПЕРСПЕКТИВЫDedovI. I.ДедовИ. И.
Russian Federation

PhD, Professor, Academician, Russian Academy of Medical Sciences, President of Russian Academy of Medical Sciences, Director, FSBI «Endocrinological Scientific Center», Ministry of Health, Russian Federation. Address: 117036, Moscow, Dmitriy Ulyanov str. 11; Tel.: (499) 124-43-00

dedov@endocrincentr.ruTyul'pakovA. I.ТюльпаковА. Н.
Russian Federation

PhD, Head of Inherited Endocrinopathies, FSBI «Endocrinological Scientific Center», Ministry of Health, Russian Federation. Address: 117036, Moscow, Dmitriy Ulyanov str. 11; Tel.: (499) 612-77-40

ant@endocrincentr.ruChekhoninV. P.ЧехонинВ. П.
Russian Federation

PhD, Professor, Academician, Russian Academy of Medical Sciences, Academician-Secretary, Department of Medical And Biological Sciences, Head of Chair of Medical Nano Biotechnologies, SBEI HPE «Russian National Research Medical University named after N.I. Pirogov», Ministry of Health, Russian Federation. Address: 117997, Moscow, Ostrovityanova str. 1. Tel.: (495) 434-04-56

chekhoninnew@yandex.ruBaklaushevV. P.БаклаушевВ. П.
Russian Federation

Candidate of Medical Sciences, Associate Professor, Chair of Medical Nano Biotechnologies, SBEI HPE «Russian National Research Medical University named after N.I. Pirogov», Ministry of Health, Russian Federation. Address: 117997, Moscow, Ostrovityanova str. 1. Tel.: (495) 434-13-01

serpoff@gmail.comArchakovA. I.АрчаковА. И.
Russian Federation

PhD, Professor, Academician, Russian Academy of Medical Sciences, Vice-President of Russian Academy of Medical Sciences, Director, FSBI «Scientific Research Institute of Biomedical Chemistry named after V.N. Orekhovich», Russian Academy of Medical Sciences. Address: 119121, Russia, Moscow, Pogodinskaya str. 10. Tel.: (499) 246-69-80

inst@ibmc.msk.ruMoshkovskiiS. A.МошковскийС. А.
Russian Federation

PhD, Head of Proteom Studies Department, FSBI «Scientific Research Institute of Biomedical Chemistry named after V.N. Orekhovich», Russian Academy of Medical Sciences. Address: 119121, Russia, Moscow, Pogodinskaya str. 10. Tel./Fax: (499) 245-08-57

smosh@mail.ruEndocrinology State Research Center of the Ministry of Health and Social Development of the Russian FederationЭндокринологический научный центр МЗ РФ, Москва, Российская ФедерацияState Budgetary Educational Institution of High Professional Education «N.I. Pirogov Russian National Research Medical University» of Ministry of Health of Russian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. Пирогова МЗ РФ, Москва, Российская ФедерацияV.N. Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical SciencesНаучно-исследовательский институт биомедицинской химии им. В.Н. Ореховича РАМН, Москва, Российская Федерация101220126712Вестник Российской академии медицинских наук41207082015Copyright ©; 2012, "Paediatrician" Publishers LLCCopyright ©; 2012, Издательство "Педиатръ"2012"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/229

A review describes general trends and directions of personalized medicine. These include, but not limited to, prediction of disease based on genomic data, diagnostics and therapy monitoring using genomic and postgenomic technologies as well as therapeutic drug monitoring and regenerative cell technologies. The personalized medicine is considered in terms of results of the Human Genome Project and succeeding Human Proteome Project. An importance of personalized approach for modern medicine is emphasized.

В обзоре описаны основные тенденции и направления персонализированной медицины. Они включают предсказание на основе геномных данных вероятности возникновения того или иного заболевания, диагностику заболевания и выбор тактики лечения с использованием геномных и постгеномных технологий, а также терапевтический лекарственный мониторинг и регенеративные клеточные технологии. Персонализированная медицина рассматривается в аспекте результатов проекта «Геном человека» и следующего за ним проекта «Протеом человека». Подчеркивается значимость развития персонализированного подхода в современной медицине.

personalized medicinegenomicsproteomicsmetabolomicstherapeutic drug monitoringперсонализированная медицинагеномикапротеомикаметаболомикатерапевтический лекарственный мониторинг1. DeGoma E.M., Rivera G., Lilly S.M., et al. Personalized vascular medicine: individualizing drug therapy. Vascular. Med 2011; 16(5): 391-404.2. Hamburg M.A., Collins F.S. The path to personalized medicine. N. Engl. J. Med. 2010; 363 (4): 301-304.3. Chan I.S., Ginsburg G.S. Personalized medicine: progress and promise. Annu Rev. Genomics Hum. Genet 2011; 12: 217-244.4. Jain K.K. From molecular diagnostics to personalized medicine. Exp. Rev. Mol. Diagn 2002; 2(4):299-301.5. Jain K.K. Nanobiotechnology and personalized medicine. Prog. Mol. Biol. Transl. Sci 2011; 104:325-54.6. de Miranda D.M., Mamede M., de Souza B.R., et al. Molecular medicine: a path towards a personalized medicine. Rev. Bras Psiquiatr 2012; 34(1): 82-91.7. Whitcomb D.C. Going MAD: development of a "matrix academic division" to facilitate translating research to personalized medicine. Acad. Med. 2011; 86(11):1353-1359.8. Scudellari M. Genomics contest underscores challenges of personalized medicine. Nat. Med. 2012; 18(3): 326.9. Hoggatt J. Personalized medicine--trends in molecular diagnostics: exponential growth expected in the next ten years. Mol. Diagn. Ther. 2011; 15(1):53-55.10. Hodgson D.R., Wellings R., Harbron C. Practical perspectives of personalized healthcare in oncology. N Biotechnol 2012; Mar 15. (Epub ahead of print).11. Thomson A. Why do therapeutic drug monitoring. The Pharm. Journal. 2004; 273:153-155.12. Baltimore D. Our genome unveiled. Nature 2001; 409(6822):814–816.13. Lander E.S., Linton L.M., Birren B., et al. Initial sequencing and analysis of the human genome. Nature 2001; 409 (6822): 860–921.14. Peltonen L., McKusick V.A. Dissecting human disease in the postgenomic era. Science. 2001; 291(5507):1224–1229.15. Kaiser J. The Genome Project: What Will It Do as a Teenager? Science. 2011; 331(6018):660.16. Johnson A.D., O’Donnell C.J. An open access database of genome-wide association results. BMC Med. Genet. 2009; 10: 6.17. Thompson A.J., Muir A.J., Sulkowski M.S., et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010; 139 (1):120–129.18. Link E., Parish S., Armitage J., et al. SLCO1B1 variants and statin-induced myopathy: a genomewide study. N. Engl. J. Med 2008; 359 (8):789–799.19. Nebert D.W., Zhang G. Personalize medicine: temper expectations. Science. 2012, 337(6097):910.20. Archey W.B., McEachern K.A., Robson M., et al. Increased CpG methylation of the estrogen receptor gene in BRCA1-linked estrogen receptor-negative breast cancers. Oncogene. 2002; 21(46):7034–7041.21. Devaskar S.U., Thamotharan M. Metabolic programming in the pathogenesis of insulin resistance. Rev. Endocr. Metab. Disord. 2007; 8(2):105–113.22. Corwin E.J. The concept of epigenetics and its role in the development of cardiovascular disease: commentary on “New and emerging theories of cardiovascular disease.” Biol. Res. Nurs 2004; 6(1):11–16, 21–23.23. Futreal P.A., Coin L., Marshall M., et al. A census of human cancer genes. Nat. Rev. Cancer 2004; 4 (3): 177–183.24. Garber K. Human Cancer Genome Project moving forward despite some doubts in community. J. Nat. Cancer Inst 2005; 97(18):1322–24.25. Golub T.R., Slonim D.K., Tamayo P., et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999; 286(5439):531–37.26. Newell K.A., Asare A., Kirk A.D., et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J. Clin. Investig. 2010; 120 (6):1836–1847.27. Rosenberg S., Elashoff M.R., Beineke P., et al. Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann. Intern. Med. 2010; 153(7):425–434.28. Klein T.E., Altman R.B., Eriksson N., et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N. Engl. J. Med. 2009; 360(8):753–764.29. Moyer V.A., U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann. Intern Med 2012; 157(2):120-134.30. Van’t Veer L.J.,Dai H., van de Vijver M.J., et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415 (6871): 530–536.31. Bartel D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116 (2):281–297.32. Jopling C.L., Yi M., Lancaster A.M., et al. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science. 2005; 309(5740): 1577–1581.33. Jain K.K. Role of pharmacoproteomics in the development of personalized medicine. Pharmacogenomics. 2004; 5 (3): 331-336.34. Archakov A., Aseev A., Bykov V., et al. Gene-centric view on the human proteome project: the example of the Russian roadmap for chromosome 18. Proteomics. 2011; 11(10):1853-1856.35. Rauser S., Deininger S.O., Suckau D., et al. Approaching MALDI molecular imaging for clinical proteomic research: current state and fields of application. Expert Review of Proteomics. 2010; 7(6):927-941.36. Reddy P.J., Jain R., Paik Y.K., et al. Personalized Medicine in the Age of Pharmacoproteomics: A Close up on India and Need for Social Science Engagement for Responsible Innovation in Post-Proteomic Biology. Curr. Pharmacogenomics Person Med. 2011; 9(1):67–75.37. Karpova M.A., Moshkovskii S.A., Toropygin I.Y., Archakov A.I. Cancer-specific MALDI-TOF profiles of blood serum and plasma: biological meaning and perspectives. J. Proteomics. 2010; 73(3): 537-551.38. Hyung S.W., Lee M.Y., Yu J.H., et al. A serum protein profile predictive of the resistance to neoadjuvant chemotherapy in advanced breast cancers. Mol. Cell. Proteomics. 2011; 10 (10): M111.011023.39. Sakamoto J.H., van de Ven A.L., Godin B., et al. Enabling individualized therapy through nanotechnology. Pharmacol. Res. 2010; 62(2):57-89.40. Leth-Larsen R., Lund R.R., Ditzel H.J. Plasma membrane proteomics and its application in clinical cancer biomarker discovery. Mol. Cell. Proteomics. 2010; 9(7):1369-1382.41. Chumbalkar V.C., Subhashini C., Dhople V.M., et al. Differential protein expression in human gliomas and molecular insights. Proteomics. 2005; 5(4):1167–1177.42. Young J., Stone W.L. Pediatric proteomics: an introduction. Front Biosci 2012; 4:1078-1087.43. Rajaraman P., Melin B.S., Wang Z., et al. Genome-wide association study of glioma and meta-analysis. Hum Genet. 2012 [Epub ahead of print].44. Archakov A.I., Ivanov Y.D., Lisitsa A. V., Zgoda V.G. AFM fishing nanotechnology is the way to reverse the Avogadro number in proteomics. Proteomics. 2007. 7(1):4-9.45. Zgoda V.G., Kopylov A.T., Lisitsa A.V. Combined use of irreversible binding and multiple reaction monitoring technology for low- and ultra-low copy-number protein detection and quantitation. J. Proteomics. In press.46. Lapuk A.V., Wu C., Wyatt A.W., et al. From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer. J. Pathol. 2012; 227 (3): 286-297.47. Su Z.D., Sun L., Yu D.X., et al. Quantitative detection of single amino acid polymorphisms by targeted proteomics. J. Mol. Cell. Biol. 2011; 3 (5):309-115.48. Omenn G.S., Yocum A.K., Menon R. Alternative splice variants, a new class of protein cancer biomarker candidates: findings in pancreatic cancer and breast cancer with systems biology implications. Dis. Markers. 2010; 28(4): 241-251.49. Serkova N.J., Brown M.S. Quantitative analysis in magnetic resonance spectroscopy: from metabolic profiling to in vivo biomarkers. Bioanalysis. 2012; 4(3):321-341.50. Sreekumar A., Poisson L.M., Rajendiran T.M., et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009. 457 (7231): 910-914.51. Lokhov P.G., Dashtiev M.I., Moshkovskii S.A, Archakov A.I. Metabolite profiling of blood plasma of patients with prostate cancer. Metabolomics. 2009; 6(1):156–163.52. Marko-Varga G. BioBanking – The Holy Grail of novel drug and diagnostic developments? J. Clin. Bioinforma. 2011; 1 (1):14.53. Botti G., Franco R., Cantile M., et al. Tumor biobanks in translational medicine. J Transl Med. 2012; 10(1): 204.54. Chen R., Mias G.I., Li-Pook-Than J., et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell. 2012; 148 (6):1293-1307.55. Pakharukova N. A., Pastushkova L. Kh., Trifonova O. P., et al. Variability subproteoma low molecular weight serum of a healthy person in normal life. Fiziologiya cheloveka = Human Physiology. 2011. 37 (2): 77-85.56. Samot J., Moon S., Shao L., et al. Blood banking in living droplets. PLoS One. 2011; 6(3): e17530.57. Patel A. Tissue banking for research bench to bedside and back--myth, reality or fast fading reality at the dawn of a personalised healthcare era. Cell. Tissue Bank. 2011; 12(1): 19-21.58. Dillner J., Andersson K. Biobanks collected for routine healthcare purposes: build-up and use for epidemiologic research. Methods Mol. Biol. 2011; 675:113-25.59. Gibson W.M. Can Personalized Medicine Survive? Can. Fam. Physician 1971; 17 (8):29-88.60. Arnold R.M., Forrow L. Rewarding medicine: good doctors and good behavior. Ann. Intern. Med. 1990; 113(10): 794-798.61. Jain K.K. Personalized medicine. Waltham: Decision Resources Inc, 1998.62. Marshall W.J., Bangert S.K. Clinical Chemistry, 6th Edition. Edinburgh, London: Mosby Elsevier, 2008.63. Miroshnichenko I.I. Ratsional'noe dozirovanie i monitoring lekarstvennykh sredstv [Efficient Monitoring and Dosing of Medicines]. Moscow, Meditsinskoe informatsionnoe agentstvo, 2011.64. Patsalos P.N., Berry D.J., Bourgeois B.F., et al. Antiepileptic drugs - best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008; 49(7):1239–1276.65. Schwenger E., Dumontet J., Ensom M.H. Does olanzapine warrant clinical pharmacokinetic monitoring in schizophrenia? Clin. Pharmacokinet. 2011; 50 (7):415-428.66. D'Souza R., Rajji T.K., Mulsant B.H., Pollock B.G. Use of lithium in the treatment of bipolar disorder in late-life. Curr. Psychiatry Rep. 2011; 13 (6): 488-492.67. Touw D.J., Westerman E.M., Sprij A.J. Therapeutic drug monitoring of aminoglycosides in neonates. Clin. Pharmacokinet. 2009; 48(2):71-88.68. Dartois V., Barry C.E. Clinical pharmacology and lesion penetrating properties of second- and third-line antituberculous agents used in the management of multidrug-resistant (MDR) and extensively-drug resistant (XDR) tuberculosis. Curr. Clin. Pharmacol. 2010; 5 (2): 96-114.69. Pieri M., Miraglia N., Polichetti G., et al. Analytical and pharmacological aspects of therapeutic drug monitoring of mTOR inhibitors. Curr. Drug. Metab. 2011; 12(3):253-267.70. Walenga J.M., Hoppensteadt D.A. Monitoring the new antithrombotic drugs. Semin Thromb. Hemost 2004; 30(6): 683-695.71. Wiseman J.M., Evans C.A., Bowen C.L., Kennedy J.H. Direct analysis of dried blood spots utilizing desorption electrospray ionization (DESI) mass spectrometry. Analyst 2010; 135 (4): 720-725.72. Pene F., Courtine E., Cariou A., Mira J.P. Toward theranostics. Crit. Care Med. 2009. 37:S50–S58.73. Sychev D.A., Mikheeva Yu.A., Kropacheva E.S. et al. Effect of CYP2C9 gene polymorphism on the pharmacokinetics and pharmacodynamics of warfarin in patients with persistent a trial fibrillation. Klinicheskaya meditsina = Clinical Medicine. 2007; 1: 57-60.74. Search Collaborative Group, Link E., Parish S., et al. SLCO1B1 variants and statin-induced myopathy – a genomewide study. N. Engl. J. Med. 2008; 359 (8):789–799.75. Ford L.T., Berg J.D. Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. J. Clin. Pathol. 2010; 63 (4): 288-295.76. Rauch A, Rohrbach J, Bochud PY. The recent breakthroughs in the understanding of host genomics in hepatitis C. Eur. J. Clin. Invest. 2010; 40(10):950-959.77. Bibeau F., Louvet C., Afchain P., et al. Observational study on conditions for access to the analysis of KRAS mutation in patients with metastatic colorectal cancer receiving panitumumab treatment. Bull. Cancer. 2012 [Epub ahead of print].78. Jennings B., Hadfield J.E., Worsley S.D., et al. A differential PCR assay for the detection of c-erbB 2 amplification used in a prospective study of breast cancer. Molecular Pathology. 1997. 50(5): 254–256.79. Li H.W., Sykes M. Emerging concepts in haematopoietic cell transplantation. Nat. Rev. Immunol 2012; 12 (6):403-416.80. Herbert K.E., Levesque J.P., Mills A.K., et al. How we mobilize haemopoietic stem cells. Intern. Med. J. 2011; 41(8): 588-594.81. Wlodarski K.H. Haematopoietic and osteogenic bone marrow stem cells. Ortop Traumatol. Rehabil. 2011; 13(5):439-447.82. Greco S.J., Rameshwar P. Mesenchymal stem cells in drug/gene delivery: implications for cell therapy. Ther. Deliv. 2012; 3 (8): 997-1004.83. Ming G.L., Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011; 70(4):687-702.84. Roh J.K., Jung K.H., Chu K. Adult stem cell transplantation in stroke: its limitations and prospects. Curr. Stem. Cell. Res. Ther. 2008; 3 (3): 185-196.85. Prasad K., Mohanty S., Bhatia R., et al. Autologous intravenous bone marrow mononuclear cell therapy for patients with subacute ischaemic stroke: A pilot study. Indian J. Med. Res. 2012; 136 (2): 221-228.86. Pal S.N., Kofidis T. New cell therapies in cardiology. Expert Rev. Cardiovasc. Ther. 2012; 10 (8): 1023-1037.87. Sng J., Lufkin T. Emerging Stem Cell Therapies: Treatment, Safety, and Biology. Stem. Cells International. 2012 (Epub).88. Fulle S., Centurione L., Mancinelli R., et al. Stem cell ageing and apoptosis. Curr. Pharm. 2012; 18 (13): 1694-1717.89. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126 (4): 663-676.90. Robinton D.A., Daley G.Q. The promise of induced pluripotent stem cells in research and therapy. Nature. 2012; 481(7381):295-305.91. Zineh I., Huang S.M. Biomarkers in drug development and regulation: a paradigm for clinical implementation of personalized medicine. Biomark Med. 2011; 5 (6):705-713.92. Nishiyama M. Personalized medicine and molecular targets of drugs. Nihon Rinsho. 2010; 68 (10): 1917-1922.93. Mirnezami R., Nicholson J., Darzi A. Preparing for precision medicine. N. Engl. J. Med. 2012; 366 (6): 489-491.94. Swenerton K.D., Santos J.L., Gilks C.B., et al. Histotype predicts the curative potential of radiotherapy: the example of ovarian cancers. Ann. Oncol. 2011; 22 (2): 341-347.95. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; doi:10.1038/nature11412. Epub ahead of print.96. Menon R., Omenn G.S. Proteomic characterization of novel alternative splice variant proteins in human epidermal growth factor receptor 2/neu-induced breast cancers. Cancer Res. 2010; 70 (9): 3440-3449.