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DOI: 10.1055/s-0031-1274528
© Georg Thieme Verlag KG Stuttgart · New York
Pharmakogenomik: Hype oder Hope?
Pharmacogenomics: hype or hope ?Publikationsverlauf
eingereicht: 6.1.2011
akzeptiert: 21.2.2011
Publikationsdatum:
01. März 2011 (online)

Zusammenfassung
Die Pharmakogenomik propagiert ein Konzept der individualisierten Medizin, bei der jeder Patient eine zielgerichtete und maßgeschneiderte Therapie erhalten soll. Durch die Errungenschaften der Genomforschung wird es möglich, bisher unbekannte genetische Faktoren für die Pathogenese und die Progression von Erkrankungen zu identifizieren und zielgerichtete Therapieoptionen neu zu definieren. Daten zur Validität und dem klinischen Nutzen pharmakogenetischer Tests müssen bereitgestellt werden. Die Implementierung der Pharmakogenomik in die klinische Praxis ist eine der wichtigsten Aufgaben für die Zukunft, die die Etablierung von Netzwerkstrukturen unter Einbindung verschiedenster Berufsgruppen erforderlich macht.
Abstract
Pharmacogenomics follows the concept of individualized medicine via targeted and tailored therapy for each patient. This is aided by current progress in human genome research that provided the basis to link genetic markers with pathogenesis and progression for the definition of new therapy options. To achieve this it will be necessary to show the validity and clinical utility of pharmacogenomic tests prior to release. The implementation of pharmacogenomics into clinical practise is a momentous future challenge that requires the establishment of interdisciplinary networks and professional organizations.
Schlüsselwörter
Pharmakogenomik - Pharmakogenetik - personalisierte Medizin - Gendiagnostik - Biomarker
Keywords
pharmacogenomics - pharmacogenetics - personalized medicine - gene diagnostics - biomarker
Literatur
- 1 Altman R B, Kroemer H K, McCarty C A, Ratain M J, Roden D. Pharmacogenomics: will the promise be fulfilled?. Nat Rev Genet. 2011; 12 69-73
- 2 Ashley E A, Butte A J, Wheeler M T. et al . Clinical assessment incorporating a personal genome. Lancet. 2010; 375 1525-35
- 3 Biomarkers Definitions Working Group . Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001; 69 89-95
- 4 Brauch H, Mürdter T E, Eichelbaum M, Schwab M. Pharmacogenomics of Tamoxifen Therapy. Clin Chem. 2009; 55 1770-1782
- 5 Contopoulos-Ioannidis D G, Ntzani E, Ioannidis J P. Translation of highly promising basic science research into clinical applications. Am J Med. 2003; 114 477-484
- 6 Collins F S, McKusick V A. Implications of the Human Genome Project for medical science. J Am Med Assoc. 2001; 285 540-544
- 7 Evans W E, Hon Y Y, Bomgaars L. et al . Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. Clin Oncol. 2001; 19 2293-2301
-
8 FDA .Promoting
Safe and Effective Genetic Testing in the United States. The Final
Report of the Task Force on Genetic Testing. http://www.genome.gov/10001733 (last access date 4.1.2011)
- 9 Francke A L, Smit M C, de Veer A J, Mistiaen P. Factors influencing the implementation of clinical guidelines for health care professionals: a systematic meta-review. BMC Med Inform Decis Mak. 2008; 8 38
- 10 Gage B F, Eby C, Johnson J A. et al . Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008; 84 326-331
- 11 Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients’ care. Lancet. 2003; 362 1225-1230
- 12 Guessous I, Gwinn M, Yu W. et al . Trends in pharmacogenomic epidemiology: 2001 – 2007. Public Health Genomics. 2009; 12 142-148
- 13 Gurwitz D, Zika E, Hopkins M M. et al . Pharmacogenetics in Europe: barriers and opportunities. Public Health Genomics. 2009; 12 134-141
- 14 Haddow J E, Palomaki G E ACCE: a model process for evaluating data on emerging genetic tests. . In: Khoury M J, Little J, Burke W Human genome epidemiology.. Oxford: Oxford University Press; 2004: 217-233
- 15 Hartford C, Vasquez E, Schwab M. et al . Differential effects of targeted disruption of thiopurine methyltransferase on mercaptopurine and thioguanine pharmacodynamics. Cancer Res. 2007; 67 4965-72
- 16 Heard E, Tishkoff S, Todd J A. et al . Ten years of genetics and genomics: what have we achieved and where are we heading?. Nat Rev Genet. 2010; 11 723-733
- 17 Holmes M V, Shah T, Vickery C, Smeeth L, Hingorani A D, Casas J P. Fulfilling the promise of personalized medicine?. PLoS One. 2009; 4 e7960
-
18 The Great Beyond. Consumer genomics
company snafu. June 07, 2010. http://blogs.nature.com/news/thegreatbeyond/2010/06/consumer_genomics_company_snaf_1.html (last access date 4.1.2011)
-
19 U.S. System of Oversight of Genetic
Testing: A Response to the Charge of the Secretary of Health and
Human Services Report of the Secretary’s Advisory Committee
on Genetics, Health, and Society. http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_oversight_report.pdf (last access date 4.1.2011)
-
20 SNPExpress .What
is SNPExpress?. http://people.genome.duke.edu/∼dg48/SNPExpress/index.php (last access date 4.1.2011)
-
21 International HapMap Project. http://snp.cshl.org/cgi-perl/gbrowse/hapmap27_B36/ (last
access date 4.1.2011)
- 22 Hughes A R, Spreen W R, Mosteller M. et al . Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to confirmation to clinical utility. Pharmacogenomics J. 2008; 8 365-74
- 23 Ikediobi O N, Shin J, Nussbaum R L, Phillips K A, Walsh J M, Ladabaum U, Marshall D. UCSF Center for Translational and Policy Research on Personalized Medicine . Addressing the challenges of the clinical application of pharmacogenetic testing. Clin Pharmacol Ther. 2009; 86 28-31
- 24 Klein T E, Altman R B. International Warfarin Pharmacogenetics Consortium . Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009; 360 753-64
- 25 Kerb R, Schwab M Impact of pharmacogenetics on drug-drug interactions.. In: Pang S K, Rodrigues D A, Peter R M Enzymatic- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges.. New York: Springer; 2010: 51-74
- 26 Kirchheiner J, Schwab M Heterogeneity of Drug Responses and Individualization of Therapy (Chapter 16). . In: Pharmacology and Therapeutics. Principles to Practice.. Philadelphia: Elsevier; 2008: 225-238
- 27 Khoury M J, Feero W G, Reyes M. et al . The genomic applications in practice and prevention network. Genet Med. 2009; 11 488-494
- 28 Khoury M J. Dealing with the evidence dilemma in genomics and personalized medicine. Clin Pharmacol Ther. 2010; 87 635-638
- 29 Little J, Higgins J P, Ioannidis J P. et al . STrengthening the REporting of Genetic Association studies (STREGA): an extension of the STROBE Statement. Ann Intern Med. 2009; 150 206-215
- 30 Ng P C, Zhao Q, Levy S, Strausberg R L, Venter J C. Individual genomes instead of race for personalized medicine. Clin Pharmacol Ther. 2008; 84 306-309
- 31 Ng P C, Murray S S, Levy S, Venter J C. An agenda for personalized medicine. Nature. 2009; 461 724-726
- 32 Petitti D B, Teutsch S M, Barton M B, Sawaya G F, Ockene J K, DeWitt T. U.S. Preventive Services Task Force . Update on the methods of the U.S. Preventive Services Task Force: insufficient evidence. Ann Intern Med. 2009; 150 199-205
- 33 Phillips E, Mallal S. Successful translation of pharmacogenetics into the clinic: the abacavir example. Mol Diagn Ther. 2009; 13 1-9
- 34 Rogowski W H, Grosse S D, Khoury M J. Challenges of translating genetic tests into clinical and public health practice. Nat Rev Genet. 2009; 10 489-495
- 35 Sawaya G F, Guirguis-Blake J, LeFevre M, Harris R, Petitti D. U.S. Preventive Services Task Force . Update on the methods of the U.S. Preventive Services Task Force: estimating certainty and magnitude of net benefit. Ann Intern Med. 2007; 147 871-875
- 36 Schaeffeler E, Stanulla M, Greil J. et al . A novel TPMT missense mutation associated with TPMT deficiency in a five year old boy with ALL. Leukemia. 2003; 17 1422-1424
- 37 Schaeffeler E, Fischer C, Brockmeier D. et al . Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics. 2004; 14 407-417
- 38 Schaeffeler E, Zanger U M, Eichelbaum M, Asante-Poku S, Shin J -G, Schwab M. Highly multiplexed genotyping of thiopurine S-methyltransferase variants using MALDI-TOF mass spectrometry: reliable genotyping in different ethnic groups. Clin Chem. 2008; 54 1637-1647
- 39 Schroth W, Goetz M P, Hamann U. et al . Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. J Am Med Assoc. 2009; 302 1429-1436
- 40 Schwab M, Schaeffeler E, Marx C, Zanger U M, Aulitzky W, Eichelbaum M. Shortcoming in the diagnosis of thiopurine S-methyltransferase deficiency by using phenotyping. Gastroenterology. 2001; 121 500-501
- 41 Schwab M, Marx C, Zanger U M, Eichelbaum M. Pharmakogenetik der Cytochrom P-450 Enzyme: Bedeutung für Wirkung und Nebenwirkung von Medikamenten. Dtsch Ärztebl. 2002; 99 A497-504
- 42 Stanulla M, Schaeffeler E, Möricke A. et al . Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukaemia on Berlin-Frankfurt-Münster protocols. Blood. 2009; 114 1314-1318
- 43 Teml A, Schaeffeler E, Herrlinger K R, Klotz U, Schwab M. Thiopurine treatment in inflammatory bowel disease: Clinical pharmacology and implication of pharmacogenetically-guided dosing. Clin Pharmacokinetics. 2007; 46 187-208
- 44 Teml A, Schaeffeler E, Schwab M. Pretreatment determination of TPMT – state of the art in clinical practice. Eur J Clin Pharmacol. 2009; 65 219-221
- 45 Wagner A K, Chan K A, Dashevsky I. et al . FDA drug prescribing warnings: is the black box half empty or half full?. Pharmacoepidemiol Drug Saf. 2006; 15 369-386
-
46 Agency for Healthcare Research
and Quality .U.S. Preventive Services Task Force (USPSTF). www.ahrq.gov/clinic/uspstfix.htm (last access
date 4.1.2011)
-
47 Centers for Disease Control
and Prevention .Public Health Genomics: Genomic Testing.
ACCE Model Process for Evaluating Genetic Tests. www.cdc.gov/genomics/gtesting/ACCE/index.htm (last access date 4.1.2011)
-
48 Centers for Disease Control
and Prevention .Public Health Genomics: Genomics Translation:
Genomic Applications in Practice and Prevention Network (GAPPNet™).
www.cdc.gov/genomics/translation/GAPPNet/index.htm (last access date 4.1.2011)
-
49 Evaluation of Genomic Applications
in Practice and Prevention (EGAPP). www.egappreviews.org/default.htm (last access date 4.1.2011)
-
50 Evaluation of Genomic Applications
in Practice and Prevention (EGAPP). Working Group: Evidence Reports
. www.egappreviews.org/workingrp/reports.htm (last
access date 4.1.2011)
-
51 The European Medicines Agency .The European Medicines Agency Road Map to 2010: Preparing the
Ground for the Future. Executive Summary. www.emea.europa.eu/pdfs/general/direct/directory/3416303enF.pdf (last
access date 4.1.2011)
-
52 U.S. Food and Drug Administration .Table of Pharmacogenomic Biomarkers in Drug Labels. www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm (last access date 4.1.2011)
-
53 U.S. Food and Drug Administration .For consumers: Important safety-related label update for Ziagen
(abacavir sulfate). www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm121646.htm (last access date 4.1.2011)
-
54 U.S. Food and Drug Administration .FDA's Critical Path Initiative. www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/ucm076689.htm (last access date 19.02.2011)
-
55 U.S: Government Printing
Office .Public Law 110 – 233 – Genetic
Information Nondiscrimination Act of 2008 . www.gpo.gov/fdsys/pkg/PLAW-110publ233/content-detail.html (last access date 4.1.2011)
-
56 HuGE Navigator. An integrated,
searchable knowledge base of genetic associations and human genome
epidemiology. . www.hugenavigator.net/ (last access date
4.1.2011)
-
57 GAPP Knowledge Base. An integrated,
searchable knowledge base of genomic applications in practice and
prevention (GAPP). www.hugenavigator.net/GAPPKB/home.do (last access date 4.1.2011)
-
58 GANI_MED. Greifswald
Approach to Individualized Medicine. www.medizin.uni-greifswald.de/gani_med/ (last
access date 4.1.2011)
-
59 National Center for Biotechnology
Information .Single Nucleotide Polymorphism. www.ncbi.nlm.nih.gov/projects/SNP/ (last
access date 4.1.2011)
-
60 Pathway Genomics. Drug Response
(Medication). www.pathway.com/more_info/drug_responses (last access date 4.1.2011)
-
61 Wellcome Trust Sanger Institute .NCI-60 Cancer Cell Line Mutation Data. www.sanger.ac.uk/genetics/CGP/NCI60/ (last
access date 4.1.2011)
-
62 Warfarin Dosing. www.warfarindosing.org/Source/Home.aspx (last access date 4.1.2011)
-
63 23andMe .Genetics
just got personal. www.23andme.com (last access date 4.1.2011)
-
64 23andMe. Advisory board. . www.23andme.com/about/advisors/ (last
access date 4.1.2011)
-
65 1000 Genomes. A Deep Catalog
of Human Genetic Variation. www.1000genomes.org/ (last
access date 4.1.2011)
- 66 Yu W, Gwinn M, Clyne M, Yesupriya A, Khoury M J. A navigator for human genome epidemiology. Nat Genet. 2008; 40 124-125
- 67 Zanger U M, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem. 2008; 392 1093-108
- 68 Zanger U M. Pharmacogenetics – challenges and opportunities ahead. Front Pharmacol. 2010; 1 112 DOI: 10.3389/fphar.2010.00112
Prof. Dr. Matthias Schwab
Dr. Margarete Fischer-Bosch Institut für
Klinische Pharmakologie
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112
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