domingo, 2 de marzo de 2014

Clinical Pharmacology & Therapeutics - Clinical Implementation of Germ Line Cancer Pharmacogenetic Variants During the Next-Generation Sequencing Era

Clinical Pharmacology & Therapeutics - Clinical Implementation of Germ Line Cancer Pharmacogenetic Variants During the Next-Generation Sequencing Era



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Clinical Pharmacology & Therapeutics (2014); 95 3, 269–280. doi:10.1038/clpt.2013.214

Clinical Implementation of Germ Line Cancer Pharmacogenetic Variants During the Next-Generation Sequencing Era

N K Gillis1, J N Patel1,2 and F Innocenti1,3
  1. 1Division 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. 2Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina, USA
  3. 3Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Correspondence: F Innocenti, (innocent@email.unc.edu)
Received 6 September 2013; Accepted 12 October 2013
Accepted article preview online 17 October 2013; Advance online publication 15 January 2014

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.

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