Toxicogenomics in the Pharmaceutical industry: Differential Gene Expression as it Relates to Histopathological Tissue Alterations in Toxicology Studies

摘要

Assessing the toxic potential of xenobiotics in the pharmaceutical industry has historically been a very costly and labor intensive process. The toxicological liabilities of new chemical entities declared for development may not be fully realized until the compound is well into the development process. The conventional approach for new drug development in toxicology includes mutagenic and toxicokinetic toxicity testing, range-finding and subchronic studies, as well as two 2-year carcinogenicity bioassays in two rodent species (rat and mouse) for drugs with chronic indications. The failure rate of drug candidates due to adverse events in toxicology animal studies is high, and the later in the development phase of a compound that these events are discovered, the more costly. New scientific fields and technologies are emerging that will hopefully provide information to characterize and/or predict drug toxicity earlier. Traditional toxicology relies primarily on animal histopathology and clinical pathology data to characterize the toxicity of a chemical. These traditional endpoints often do not provide much information regarding mechanisms of toxicity. Additionally, they provide limited predictive value in assessing human risk in clinical trials.