Genomic Technologies for Toxicology Biomarkers
Genomics can be applied in biomarker identification as a source of candidate markers or marker panels. In toxicology, the mechanism cannot yet be deduced from expression data alone; therefore, genomic data are best utilized to provide direction into areas of research that should be pursued in the laboratory. These “functional” or “localization” studies are critical in providing validated toxicology biomarkers. Despite an abundance of candidates identified with genomic and other technologies, there is a scarcity of biomarkers that are readily applicable and interpretable alongside routine clinical chemistry in optimizing lead molecules. To validate candidate biomarkers after functional or localization studies, they must be tested in internal lead optimization studies routinely run in pharmaceutical preclinical development. Future technologies should integrate all assay types into one format that measures different analytes simultaneously regardless of whether the biomarkers are nucleic acids, proteins or metabolites. Testing in lead optimization studies provides the positive and negative control data necessary to build experience and give toxicology biomarkers meaning, so that decisions can be made from their application.