Strategic Applications of Gene Expression: From Drug Discovery/Development to Bedside
- 15 January 2013
- journal article
- review article
- Published by Springer Science and Business Media LLC in The AAPS Journal
- Vol. 15 (2), 427-437
- https://doi.org/10.1208/s12248-012-9447-1
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.Keywords
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