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Strategic Applications of Gene Expression: From Drug Discovery/Development to Bedside

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ABSTRACT

Gene expression is useful for identifying the molecular signature of a disease and for correlating a pharmacodynamic marker with the dose-dependent cellular responses to exposure of a drug. Gene expression offers utility to guide drug discovery by illustrating engagement of the desired cellular pathways/networks, as well as avoidance of acting on the toxicological pathways. Successful employment of gene-expression signatures in the later stages of drug development depends on their linkage to clinically meaningful phenotypic characteristics and requires a biologically meaningful mechanism combined with a stringent statistical rigor. Much of the success in clinical drug development is hinged on predefining the signature genes for their fitness for purposes of application. Specific examples are highlighted to illustrate the breadth and depth of the potential utility of gene-expression signatures in drug discovery and clinical development to targeted therapeutics at the bedside.

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Acknowledgment

Alexander Statnikov was supported in part by NIH/NLM grant 1 R01 LM011179-01.

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Authors and Affiliations

  1. Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    Jane P. F. Bai

  2. Center for Health Informatics and Bioinformatics, Division of Translational Medicine, Department of Medicine, New York University Langone Medical Center, New York, New York, 10016, USA

    Alexander V. Alekseyenko & Alexander Statnikov

  3. Informatics and Analysis Department, Merck Research Laboratory, 770 Sumneytown Pike, West Point, Pennsylvania, 19486, USA

    I-Ming Wang

  4. Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, New Jersey, 07065, USA

    Peggy H. Wong

Authors
  1. Jane P. F. Bai
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  2. Alexander V. Alekseyenko
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  3. Alexander Statnikov
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  4. I-Ming Wang
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  5. Peggy H. Wong
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Corresponding author

Correspondence to Jane P. F. Bai.

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Jane P.F. Bai, I-Ming Wang, and Peggy H. Wong equally contributed to this work.

The views expressed in this article by the FDA employee do not necessarily represent the views of the US Food and Drug Administration.

The views expressed in this article by the Merck employees do not necessarily represent the views of Merck & Co., Inc.

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Bai, J.P.F., Alekseyenko, A.V., Statnikov, A. et al. Strategic Applications of Gene Expression: From Drug Discovery/Development to Bedside. AAPS J 15, 427–437 (2013). https://doi.org/10.1208/s12248-012-9447-1

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  • DOI: https://doi.org/10.1208/s12248-012-9447-1

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