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PMID: 24136381 Published · ppublish English Journal Article Review

Clinical implementation of germ line cancer pharmacogenetic variants during the next-generation sequencing era.

Clinical pharmacology and therapeutics ·Vol. 95 ·No. 3 ·2014-03-00 ·Pages 269-80

Gillis NK, Patel JN, Innocenti F

Abstract

More than 100 medications approved by the US Food and Drug Administration include pharmacogenetic biomarkers in the drug label, many with cancer indications referencing germ line DNA variations. With the advent of next-generation sequencing (NGS) and its rapidly increasing uptake into cancer research and clinical practice, an enormous amount of data to inform documented gene-drug associations will be collected that must be exploited to optimize patient benefit. This review focuses on the implementation of germ line cancer pharmacogenetics in clinical practice. Specifically, it discusses the importance of germ line variation in cancer and the role of NGS in pharmacogenetic discovery and implementation. In the context of a scenario in which massive amounts of NGS-based genetic information will be increasingly available to health stakeholders, this review explores the ongoing debate regarding the threshold of evidence necessary for implementation, provides an overview of recommendations in cancer by professional organizations and regulatory bodies, and discusses limitations of current guidelines and strategies to improve third-party coverage.

MeSH Terms
Biomarkers Cost-Benefit Analysis Evidence-Based Medicine Government Agencies High-Throughput Nucleotide Sequencing/trends Humans Insurance, Health Neoplasms, Germ Cell and Embryonal/drug therapy,genetics Pharmacogenetics/trends
Chemicals
Biomarkers
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Gillis N K
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, North Carolina, USA.
Patel J N
1] Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, North Carolina, USA [2] Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina, USA.
Innocenti F
1] Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, North Carolina, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
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Article Info
Journal
Clinical pharmacology and therapeutics
Abbr.
Clin Pharmacol Ther
ISSN
1532-6535
DOI
10.1038/clpt.2013.214
Published
2014-03-00
Epub
2013-00-17
Pages
269-80
Language
English
Region
United States
NLM ID
0372741
PMCID
PMC4128332
Subset
IM
Grants
NCI NIH HHS · K07 CA140390 · United States
External Links
PubMed source DOI: 10.1038/clpt.2013.214 PMC Full Text View journal details
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