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Pharmacogenetics in drug discovery and development: a translational perspective

Nature Reviews Drug Discovery volume 7, pages 807–817 (2008)Cite this article

Abstract

The ability to predict a patient's drug response on the basis of their genetic information is expected to decrease attrition during the development of new, innovative drugs, and reduce adverse events by being able to predict individual patients at risk. Most pharmacogenetic investigations have focused on drug-metabolism genes or candidate genes that are thought to be involved in specific diseases. However, robust new genetic tools now enable researchers to carry out multi-candidate gene-association and genome-wide studies for target discovery and drug development. Despite the expanding role of pharmacogenetics in industry, however, there is a paucity of published data. New forms of effective and efficient collaboration between industry and academia that may enhance the systematic collection of pharmacogenetic data are necessary to establish genetic profiles related to drug response, confirm pharmacogenetic associations and expedite the development of new drugs and diagnostic tests.

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Figure 1: Drug discovery and development pipeline and the contribution of PGx.
Figure 2: Reducing attrition through the application of pharmacogenetics.
Figure 3: Growth of HLA-B*5701 testing between August 2007 to November 2007.

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Acknowledgements

I thank T. Yamada and J. Niedel who supported a Genetics Research Directorate within a large pharmaceutical company, and the hundreds of scientists and physicians at GlaxoSmithKline in genetics research whose dedication and work provided the impetus for the data generated as examples of pharmacogenetics projects. The support of GlaxoSmithKline during a rapidly changing period of technology growth and change had a profound impact on the formation of the SNP Consortium and the Severe Adverse Event Consortium. I also thank the Duke University School of Medicine and the Fuqua School of Business for enabling the establishment of the Deane Drug Discovery Institute as part of the Institute for Genome Sciences and Policy. The Institute operates as a virtual pharmaceutical company owned by a not-for-profit institution with no public shareholders.

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  1. Allen D. Roses is at the Deane Drug Discovery Institute, Duke University Medical Center and Fuqua School of Business, One Science Drive, Durham, North Carolina 27708, USA. allen.roses@duke.edu,

    Allen D. Roses

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Competing interests

Allen D. Roses retired from GlaxoSmithKline in October 2007 and has founded a private pharmacogenetic consultation and project management company, Cabernet Pharmaceuticals, Inc. Cabernet has multiple service contracts for pipeline PGx with several biotechnical and pharmaceutical companies. He holds stock options of GlaxoSmithKline until September 2009. He was a member of the FDA Science Board for 4 years and currently consults for the FDA.

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DATABASES

OMIM

Alzheimer's disease

Crohn's disease

non-small-cell lung cancer

type 2 diabetes mellitus

FURTHER INFORMATION

FDA Science and Mission at Risk

Guidance for Industry: E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories

Guidance for Industry and FDA. Staff Pharmacogenetic Tests and Genetic Tests for Heritable Markers

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Roses, A. Pharmacogenetics in drug discovery and development: a translational perspective. Nat Rev Drug Discov 7, 807–817 (2008). https://doi.org/10.1038/nrd2593

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