The Role of Transcriptome Analysis in Pre-Clinical Toxicology

Abstract

A major benefit of the genomics revolution in biomedical research has been the establishment of transcriptome analysis as an enabling technology in the drug development process. Nowhere in the realm of drug development has the expectation of the impact of transcriptome analysis been greater than in the area of pre-clinical toxicology. Transcriptome analysis, along with other new high-content data generating technologies, has the potential to radically improve the drug safety assessment process by allowing drug development teams to identify potential toxicity liabilities earlier, and thus proceed only with those molecules that have both efficacy at the target and a low potential for toxicity in the human population. In this review we will briefly describe the major ways in which transcriptome analysis is being applied in the pre-clinical safety assessment process, focusing primarily on four areas where transcriptome analysis has already begun to have impact. These include using transcriptome analysis to: 1) understand mechanisms of toxicity: 2) predict toxicity: 3) develop in vivo and in vitro surrogate models and screens; and, 4) develop toxicity biomarkers. We will close by briefly addressing future trends and needs in the application of transcriptome analysis to drug safety assessment.

Drug-induced Phospholipidosis -Pathological Aspects and Its Prediction

“…Several studies have been reported using toxicogenomic techniques to examine tissue responses to toxicants [88][89][90] . Thus, now this technology is readily available it will be used more for this field of research in the near future.…”

Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database

“…Genomic data can be more sensitive and objective than traditional methods for the early prediction of compound-induced toxicity. Microarray expression profiling during preclinical drug development is expected to aid in uncovering unexpected or secondary pharmacology, predicting adverse effects, and understanding the mechanisms of drug action or toxicity (Battershill, 2005;Heinloth et al, 2004;Irwin et al, 2004;Searfoss et al, 2005).…”

Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms

“…In particular, gene expression data (transcriptomics) are thought to be more sensitive than traditional toxicological endpoints (Searfoss et al, 2005). Toxicogenomics can also help to bridge traditional in vitro and in vivo toxicity assessment (Wilson et al, in press), and could be a very effective tool in studying the safety of herbal medicines by expanding the predictivity of potential toxicity in earlier stages of product development (Amir-Aslani, 2008; Blomme et al, 2009).…”