Application of Genomics in Preclinical Drug Safety Evaluation
| Autor: | Peter Lord, Alex Nie, Michael K. McMillian |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Drug
Drug-Related Side Effects and Adverse Reactions media_common.quotation_subject Population Drug Evaluation Preclinical Genomics Computational biology Toxicology Risk Assessment Molecular level Humans Medicine education media_common Pharmacology education.field_of_study business.industry Gene Expression Profiling General Medicine Microarray Analysis Biotechnology Gene expression profiling Drug development Knowledge base Toxicogenomics business |
| Zdroj: | Basic Toxicology. 98:537-546 |
| ISSN: | 1742-7843 1742-7835 |
| DOI: | 10.1111/j.1742-7843.2006.pto_444.x |
| Popis: | Understanding the response of biological systems to xenobiotics is fundamental to the evaluation of drug safety. Toxicologists have traditionally gathered pathological, morphological, chemical and biochemical information from in vivo studies of preclinical species in order to assess drug safety and to determine how new drugs can be safely administered to the human patient population. In recent years the emerging "-omics" technologies have been developed and integrated into preclinical studies in order to better assess drug safety by gaining information on the cellular and molecular events underlying adverse drug reactions. Genomics approaches in particular have become readily available and are being applied in several stages of drug development. The burgeoning literature on what has become known as "toxicogenomics" has for the most part highlighted successful applications of gene expression profiling in predictive toxicology, enabling decisions to be made on the developability of a compound early in the drug development process. It is also becoming apparent that toxicogenomic approaches are good starting points to develop experiments designed to gain a mechanistic insight into drug toxicities within and across species. Gene expression arrays permit the measurement of responses of essentially all the genes in the entire genome to be monitored, and knowledge of the function of the genes affected can identify the potential mechanisms to then be confirmed using conventional biochemical, toxicological and pathological approaches. As toxicologists put these technologies into practice they build up a knowledge base to better characterize toxicities at the molecular level and to make the search for much needed, novel biomarkers of toxicity more achievable. |
| Databáze: | OpenAIRE |
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