Toxicogenomics: an opportunity to optimise drug development and safety evaluation.
'Toxicogenomics', the use of complex populations of mRNA to understand toxicity, is a relatively new field which combines the wealth of gene sequence information with advances in miniaturisation technology. In a parallel evolutionary path that the broader field of toxicology has encountered, toxicogenomics is steadily changing from descriptive to mechanistic research and will ultimately progress to a predictive science. This review focuses on the application of microarray research tools to toxicology studies in preclinical development. In particular, the 'testing funnel' approach to candidate selection in drug development is used to discuss the strategic implementation of toxicogenomics to help develop drugs that harbour less toxicity. Examples of where toxicogenomics has increased mechanistic and descriptive understanding of cellular toxicity are discussed, as are early efforts to develop molecular biomarkers that are predictive of longer-term toxicity.
Kramer
Jeffrey A
JA
Global Toxicology, Pharmacia Corporation, St Louis, MO 63167, USA.
Kolaja
Kyle L
KL
D000818:Animals; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends