Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects

Simona Volpi¹, Carol J Bult², Rex L Chisholm³, Patricia A Deverka⁴, Geoffrey S Ginsburg⁵, Howard J Jacob⁶, Melpomeni Kasapi¹, Howard L McLeod⁷, Dan M Roden⁸, Marc S Williams⁹, Eric D Green¹, Laura Lyman Rodriguez¹, Samuel Aronson¹⁰, Larisa H Cavallari¹¹, Joshua C Denny¹², Lynn G Dressler¹³, Julie A Johnson¹¹, Teri E Klein¹⁴, J Steven Leeder¹⁵, Micheline Piquette-Miller¹⁶, Minoli Perera¹⁷, Laura J Rasmussen-Torvik¹⁸, Heidi L Rehm¹⁹, Marylyn D Ritchie²⁰, Todd C Skaar²¹, Nikhil Wagle²², Richard Weinshilboum²³, Kristin W Weitzel²⁴, Robert Wildin²⁵, John Wilson²⁶, Teri A Manolio¹, Mary V Relling²⁷

Affiliations

¹ National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
² The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA.
³ Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
⁴ American Institutes for Research, Washington, DC, USA.
⁵ Duke Center for Applied Genomic and Precision Medicine, Duke University, Durham, North Carolina, USA.
⁶ HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
⁷ DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, Florida, USA.
⁸ Department of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁹ Genomic Medicine Institute, Geisinger, Danville, Pennsylvania, USA.
¹⁰ Partners Healthcare, Cambridge, Massachusetts, USA.
¹¹ Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA.
¹² Departments of Biomedical Informatics and Medicine, Vanderbilt University, Nashville, Tennessee, USA.
¹³ Mission Health, Personalized Medicine Program, Asheville, North Carolina, USA.
¹⁴ Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
¹⁵ Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Hospital, Kansas City, Missouri, USA.
¹⁶ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
¹⁷ Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁸ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁹ Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²⁰ Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
²¹ Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²² Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
²³ Department of Molecular Pharmacology and Experimental Therapeutics and Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
²⁴ Department of Pharmacotherapy & Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA.
²⁵ Departments of Pathology and Laboratory Medicine, and Pediatrics, University of Vermont Medical Center, Burlington, Vermont, USA.
²⁶ Optum, Eden Prairie, Minnesota, USA.
²⁷ Pharmaceutical Sciences Department, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

PMID: 29460415
PMCID: PMC5902434
DOI: 10.1002/cpt.1048

Review

Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects

Simona Volpi et al. Clin Pharmacol Ther. 2018 May.

. 2018 May;103(5):778-786.

doi: 10.1002/cpt.1048. Epub 2018 Mar 30.

Authors

Affiliations

¹ National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
² The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA.
³ Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
⁴ American Institutes for Research, Washington, DC, USA.
⁵ Duke Center for Applied Genomic and Precision Medicine, Duke University, Durham, North Carolina, USA.
⁶ HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
⁷ DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, Florida, USA.
⁸ Department of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁹ Genomic Medicine Institute, Geisinger, Danville, Pennsylvania, USA.
¹⁰ Partners Healthcare, Cambridge, Massachusetts, USA.
¹¹ Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA.
¹² Departments of Biomedical Informatics and Medicine, Vanderbilt University, Nashville, Tennessee, USA.
¹³ Mission Health, Personalized Medicine Program, Asheville, North Carolina, USA.
¹⁴ Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
¹⁵ Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Hospital, Kansas City, Missouri, USA.
¹⁶ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
¹⁷ Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁸ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁹ Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²⁰ Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
²¹ Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²² Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
²³ Department of Molecular Pharmacology and Experimental Therapeutics and Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
²⁴ Department of Pharmacotherapy & Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA.
²⁵ Departments of Pathology and Laboratory Medicine, and Pediatrics, University of Vermont Medical Center, Burlington, Vermont, USA.
²⁶ Optum, Eden Prairie, Minnesota, USA.
²⁷ Pharmaceutical Sciences Department, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

PMID: 29460415
PMCID: PMC5902434
DOI: 10.1002/cpt.1048

Abstract

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them.

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References

1. Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature. 2015;526:343–50. - PMC - PubMed
1. Cavallari LH, et al. Institutional profile: University of Florida Health Personalized Medicine Program. Pharmacogenomics. 2017;18:421–6. - PMC - PubMed
1. Garcia-Gonzalez X, Cabaleiro T, Herrero MJ, McLeod H, Lopez-Fernandez LA. Clinical implementation of pharmacogenetics. Drug Metab Pers Ther. 2016;31:9–16. - PubMed
1. Pulley JM, et al. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther. 2012;92:87–95. - PMC - PubMed
1. NHGRI. Genomic Medicine X: Research Directions in Pharmacogenomics. 2017 < https://www.genome.gov/27568408/genomic-medicine-x-pharmacogenomics>. Accessed 11/9/2017.

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Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects

Affiliations

Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources