Gene Expression-Based Biomarkers of Drug Safety

Large-scale gene expression profiling with microarray platforms represents a new approach to identify much needed, novel mechanism-based biomarkers of toxicity for use in preclinical and clinical studies. These biomarkers may have diagnostic and/or predictive values and may consist of single gene products or of gene sets or gene expression signatures. Derivation and validation of these molecular markers involves supervised classification methods of reference data with sophisticated statistical methodologies. In this chapter, we review the methods for the identification and development of toxicity biomarkers with gene expression profiling. This chapter also describes how these novel multigene molecular markers can be integrated in a discovery pipeline, using the examples of hepatotoxicity, nephrotoxicity, and blood-based markers to illustrate successful or promising applications in toxicology.