Dan M. Roden, MD; Russ B. Altman, MD, PhD; Neal L. Benowitz, MD; David A. Flockhart, MD, PhD; Kathleen M. Giacomini, PhD; Julie A. Johnson, PharmD; Ronald M. Krauss, MD; Howard L. McLeod, PharmD; Mark J. Ratain, MD; Mary V. Relling, PharmD; Huijun Z. Ring, PhD; Alan R. Shuldiner, MD; Richard M. Weinshilboum, MD; Scott T. Weiss, MD; Pharmacogenetics Research Network
Roden DM, Altman RB, Benowitz NL, Flockhart DA, Giacomini KM, Johnson JA, et al. Pharmacogenomics: Challenges and Opportunities. Ann Intern Med. 2006;145:749-757. doi: 10.7326/0003-4819-145-10-200611210-00007
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Published: Ann Intern Med. 2006;145(10):749-757.
The outcome of drug therapy is often unpredictable, ranging from beneficial effects to lack of efficacy to serious adverse effects. Variations in single genes are 1 well-recognized cause of such unpredictability, defining the field of pharmacogenetics (see Glossary). Such variations may involve genes controlling drug metabolism, drug transport, disease susceptibility, or drug targets. The sequencing of the human genome and the cataloguing of variants across human genomes are the enabling resources for the nascent field of pharmacogenomics (see Glossary), which tests the idea that genomic variability underlies variability in drug responses. However, there are many challenges that must be overcome to apply rapidly accumulating genomic information to understand variable drug responses, including defining candidate genes and pathways; relating disease genes to drug response genes; precisely defining drug response phenotypes; and addressing analytic, ethical, and technological issues involved in generation and management of large drug response data sets. Overcoming these challenges holds the promise of improving new drug development and ultimately individualizing the selection of appropriate drugs and dosages for individual patients.
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