Viewpoint | Published:

Pharmacogenomics: will the promise be fulfilled?

Nature Reviews Genetics 12, 69–73 (2011) | Download Citation

Subjects

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

Rent or Buy

All prices are NET prices.

References

  1. 1.

    et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol. 11, R82 (2010).

  2. 2.

    et al. Clinical assessment incorporating a personal genome. Lancet 375, 1525–1535 (2010).

  3. 3.

    & Clopidogrel and the concept of high risk pharmacokinetics. Circulation 119, 2127–2130 (2009).

  4. 4.

    , , & Pharmacogenomics — the genetics of variable drug responses. Circulation (in the press).

  5. 5.

    et al. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302, 1429–1436 (2009).

  6. 6.

    et al. A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nature Genet. 42, 711–714 (2010).

  7. 7.

    et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N. Engl. J. Med. 352, 2285–2293 (2005).

  8. 8.

    et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108, 2244–2247 (2006).

  9. 9.

    et al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. Blood 112, 1022–1027 (2008).

  10. 10.

    et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302, 849–857 (2009).

  11. 11.

    et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461, 399–401 (2009).

  12. 12.

    et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature Genet. 41, 816–819 (2009).

  13. 13.

    et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009).

  14. 14.

    et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809–819 (2010).

  15. 15.

    & Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nature Rev. Cancer 10, 760–774 (2010).

  16. 16.

    et al. Estimation of warfarin dose with clinical and pharmacogenetic data. N. Engl. J. Med. 360, 753–764 (2009).

  17. 17.

    & In genetic control of disease, does “race” matter? Nature Genet. 36, 1243–1244 (2004).

  18. 18.

    , & 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).

  19. 19.

    & A piece in the puzzle of personalized medicine. Clin. Pharmacol. Ther. 87, 19–20 (2010).

  20. 20.

    & Biobanking and pharmacogenomics. Pharmacogenomics 11, 637–642 (2010).

  21. 21.

    & Preprescription genotyping: not yet ready for prime time, but getting there. Circulation 103, 1608–1610 (2001).

  22. 22.

    Opportunities and challenges for the NIH—an interview with Francis Collins. Interview by Robert Steinbrook. N. Engl. J. Med. 361, 1321–1323 (2009).

Download references

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

Affiliations

  1. Russ B. Altman is at the Department of Bioengineering, Stanford University, 318 Campus Drive, S172, MC, 5444 Stanford, California 94305-5444, USA.  russ.altman@stanford.edu

    • Russ B. Altman

  2. Heyo K. Kroemer is at the Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University Greifswald, Friedrich Löfflerstrasse 23d, 17487 Greifswald, Germany.  kroemer@uni-greifswald.de

    • Heyo K. Kroemer

  3. Catherine A. McCarty is at the The Center for Human Genetics, Marshfield Clinic Research, Foundation 1000 North Oak Avenue, MLR Marshfield, Wisconsin 54449, USA.  McCarty.Catherine@mcrf.mfldclin.edu

    • Catherine A. McCarty

  4. Mark J. Ratain is at the University of Chicago Medical Center, 5841 South Maryland Avenue, MC, 2115 Chicago, Illinois 60637, USA.  mratain@medicine.bsd.uchicago.edu

    • Mark J. Ratain

  5. Dan Roden is at the Vanderbilt University School of Medicine, MRB4 1285B, 2215B Garland Avenue, Nashville, Tennessee, 37232-0575, USA.  dan.roden@Vanderbilt.Edu

    • Dan Roden

Authors

  1. Search for Russ B. Altman in:

  2. Search for Heyo K. Kroemer in:

  3. Search for Catherine A. McCarty in:

  4. Search for Mark J. Ratain in:

  5. Search for Dan Roden in:

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.

FURTHER INFORMATION

To obtain permission to re-use content from this article visit RightsLink.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrg2920

Further reading