Lord Peter G
Johnson & Johnson Pharmaceutical Research & Development LLC, 1000 Route 202, P.O. Box 300, Raritan, NJ 08869, USA.
Toxicol Lett. 2004 Apr 1;149(1-3):371-5. doi: 10.1016/j.toxlet.2003.12.045.
Genomics has had an impact on two areas of drug development, "predictive" toxicology and mechanism-based risk assessment. Predictive toxicology studies are aimed at identifying the potential for a compound to be toxic. By developing databases of expression profiles for a wide variety of toxic compounds and toxic models it has been possible to create statistical and computational methods which provide an indication of the toxic potential of a drug from the pattern of gene expression changes it elicits in in vitro or in vivo systems. Because gene expression is central to many responses to xenobiotics, genomic approaches lend themselves very readily to mechanistic toxicology studies. By examining changes in gene expression in cells and tissues in response to drugs it is possible to generate hypotheses as to the underlying mechanism and in some cases it is possible to evaluate hypotheses of toxic mechanism. Some concerns remain about the use of the technology but toxicogenomics can no longer be regarded as "new" technology in drug development. The investments made in applying the technology are maturing and there is a determined effort to bring the full power of the technology into drug development.
基因组学已对药物开发的两个领域产生了影响，即“预测性”毒理学和基于机制的风险评估。预测性毒理学研究旨在确定一种化合物产生毒性的可能性。通过建立各种有毒化合物和毒性模型的表达谱数据库，已经有可能创建统计和计算方法，这些方法可以根据药物在体外或体内系统中引发的基因表达变化模式，来指示药物的潜在毒性。由于基因表达是许多对外源化学物质反应的核心，基因组学方法非常适合用于机制毒理学研究。通过检查细胞和组织中对药物反应的基因表达变化，有可能产生关于潜在机制的假设，在某些情况下还可以评估毒性机制的假设。对于该技术的使用仍存在一些担忧，但毒理基因组学在药物开发中已不再被视为“新技术”。在应用该技术方面的投资正在成熟，并且人们正在下定决心将该技术的全部力量引入药物开发。
