Abstract
Tools such as genome resequencing and genome-wide association studies have recently been used to uncover a number of variants that affect drug toxicity and efficacy, as well as potential drug targets. But how much closer are we to incorporating pharmacogenomics into routine clinical practice? Five experts discuss how far we have come, and highlight the technological, informatics, educational and practical obstacles that stand in the way of realizing genome-driven medicine.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Jones, S.J.M. et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol. 11, R82 (2010).
Ashley, E. A. et al. Clinical assessment incorporating a personal genome. Lancet 375, 1525–1535 (2010).
Roden, D. M. & Stein, C. M. Clopidogrel and the concept of high risk pharmacokinetics. Circulation 119, 2127–2130 (2009).
Roden, D. M., Wilke, R. A., Kroemer, H. K. & Stein, C. M. Pharmacogenomics — the genetics of variable drug responses. Circulation (in the press).
Schroth, W. et al. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302, 1429–1436 (2009).
Singer, J. B. et al. A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nature Genet. 42, 711–714 (2010).
Rieder, M. J. et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N. Engl. J. Med. 352, 2285–2293 (2005).
Hulot, J. S. et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108, 2244–2247 (2006).
Cooper, G. M. et al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. Blood 112, 1022–1027 (2008).
Shuldiner, A. R. et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302, 849–857 (2009).
Ge, D. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461, 399–401 (2009).
Daly, A. K. et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature Genet. 41, 816–819 (2009).
Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009).
Flaherty, K. T. et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809–819 (2010).
Pao, W. & Chmielecki, J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nature Rev. Cancer 10, 760–774 (2010).
Klein T. E. et al. Estimation of warfarin dose with clinical and pharmacogenetic data. N. Engl. J. Med. 360, 753–764 (2009).
Goldstein, D. B. & Hirschhorn, J. N. In genetic control of disease, does “race” matter? Nature Genet. 36, 1243–1244 (2004).
Hanratty, B., Zhang, T. & Whitehead, M. How close have universal health systems come to achieving equity in use of curative services? A systematic review. Int. J. Health Serv. 37, 89–109 (2007).
Kroemer, H. K. & Meyer zu Schwabedissen, H. E. A piece in the puzzle of personalized medicine. Clin. Pharmacol. Ther. 87, 19–20 (2010).
McCarty, C. A. & Wilke, R. A. Biobanking and pharmacogenomics. Pharmacogenomics 11, 637–642 (2010).
Roden, D. M. & Brown, N. J. Preprescription genotyping: not yet ready for prime time, but getting there. Circulation 103, 1608–1610 (2001).
Collins, F. Opportunities and challenges for the NIH—an interview with Francis Collins. Interview by Robert Steinbrook. N. Engl. J. Med. 361, 1321–1323 (2009).
Acknowledgements
H.K.K.'s research is supported by the Federal Ministry of Education and Research (GANI_MED) and the Deutsche Forschungsgemeinschaft (SFB TR 19).
Author information
Authors and Affiliations
Ethics declarations
Competing interests
D.R. is a consultant for Novartis, Merck and Sanofi-Aventis in antiarrhythmic actions. He is also a consultant for Daiichii Sankyo in cardiovascular pharmacology. He receives royalties from Clinical Data, Inc., for the discovery of a potassium channel gene variant as a predictor of drug-induced arrhythmia.
Rights and permissions
About this article
Cite this article
Altman, R., Kroemer, H., McCarty, C. et al. Pharmacogenomics: will the promise be fulfilled?. Nat Rev Genet 12, 69–73 (2011). https://doi.org/10.1038/nrg2920
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrg2920
This article is cited by
-
An argument for mechanism-based statistical inference in cancer
Human Genetics (2015)
-
Practical considerations to guide development of access controls and decision support for genetic information in electronic medical records
BMC Health Services Research (2011)