Science (vol. 306, No. 5696, October 2004)


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EDITORIAL Genomics and Drug Toxicity s genomics has revolutionized the study of biology, so has it affected how drugs are discovered. Pharmaceutical companies have also realized another major application: how drugs are assessed for safety. The analysis of gene expression profiles is now actively used alongside conventional toxicological assays to assess drug safety. Such toxicogenomic analysis is being used to predict drug toxicities and to gain a more in-depth understanding of toxic mechanisms, so that more successful drug candidates can be selected. The U.S. Food and Drug Adminstration (FDA) sees genomics as a beneficial aid to the drug risk assessment process primarily through its ability to identify specific patients who are either likely to benefit from a particular drug or who may experience harm. The use of toxicogenomics also has promise in proving hypotheses that support safe drug use in humans through a mechanistic understanding of toxicities found in drug-treated animals. Take the case in which rats were treated with a certain class of hypolipidemic drugs. Changes in the expression of specific liver genes were seen that have been shown to correlate with observed liver toxicity. However, when treated human and rat liver cells were compared, analogous gene expression changes were not seen in the human cells.* Thus, by gaining a better idea of the mechanisms of toxicity in an animal species, it becomes feasible to examine species-specific effects to better assess the possible relevance of animal findings to humans. After a number of conferences and workshops based on recent FDA draft guidelines, there was agreement that some standards ought to be adopted for the generation and subsequent submission of toxicogenomic data to the FDA. This would help ensure that any regulatory decisions based on an interpretation of data can be made in a consistent manner. A number of groups are actively addr