Toxicogenomics revolution in the optimisation of pharmaceutical drug development and drug safety evaluations

摘要

Modern high throughput screening methods in toxicology need to be developed. These new approaches are necessary to provide more insight into potential human toxicity than the old traditional methods. Toxicogenomics investigate the changes in gene expression profile following exposure to a toxicant. It offers the potential to identify a human toxicant earlier in drug development and to detect human-specific toxicants that can cause no adverse reaction in rats. New transcript profiling technologies enable simultaneous measurement of the changes in expression of many hundreds or many thousands of genes. The availability of these methods has brought about significant revolutionary changes in many areas of investigative biology, where analyses of patterns of gene expression, rather than of individual genes, are being used. Toxicogenomics offers new opportunities for both mechanistic toxicity research and predictive toxicology. This paper gives an overview of the impact of toxicogenomics on the revolution of pharmaceutical drug development and drug safety evaluation. The basic approach within the frame work of high throughput screening is also a debate for discussion. The challenging issues with this novel technology in the selection screening of biomarkers for different therapeutic end points are also examined in this review.