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Toxicogenomics in Drug Development

Novartis Pharma AG, Pharmacogenomics, Preclinical Safety, Basel, Switzerland, nelson.guerreiro{at}pharma.novartis.com

Frank Staedtler

Novartis Pharma AG, Pharmacogenomics, Preclinical Safety, Basel, Switzerland

Olivier Grenet

Novartis Pharma AG, Pharmacogenomics, Preclinical Safety, Basel, Switzerland

Jeanne Kehren

Novartis Pharma AG, Pharmacogenomics, Preclinical Safety, Basel, Switzerland

Salah-Dine Chibout

Novartis Pharma AG, Pharmacogenomics, Preclinical Safety, Basel, Switzerland

Toxicogenomics represents the merging of toxicology with technologies that have been developed, together with bioinformatics, to identify and quantify global gene expression changes. It represents a new paradigm in drug development and risk assessment, which promises to generate a wealth of information towards an increased understanding of the molecular mechanisms that lead to drug toxicity and efficacy, and of DNA polymorphisms responsible for individual susceptibility to toxicity. Gene expression profiling, through the use of DNA microarray and proteomic technologies will aid in establishing links between expression profiles, mode of action and traditional toxic endpoints. Such patterns of gene expression, or `molecular fingerprints' could be used as diagnostic or predictive markers of exposure, that is characteristic of a specific mechanism of induction of that toxic or efficacious effect. It is anticipated that toxicogenomics will be increasingly integrated into all phases of the drug development process particularly in mechanistic and predictive toxicology, and biomarker discovery. This review provides an overview of the expression profiling technologies applied in toxicogenomics, and discusses the promises as well as the future challenges of applying this discipline to the drug development process.

Key Words: DNA microarrays • PCR • bioinformatics • gene expression profiling • genomics • proteomics • biomarkers • toxicology.

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Toxicologic Pathology, Vol. 31, No. 5, 471-479 (2003)
DOI: 10.1080/01926230390224656


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