Nebert Daniel W, Vesell Elliot S
Division of Human Genetics, Department of Pediatrics and Molecular Developmental Biology, Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA.
Trends Pharmacol Sci. 2006 Nov;27(11):580-6. doi: 10.1016/j.tips.2006.09.008. Epub 2006 Sep 26.
Between 1930 and 1990, several dozen high-penetrance, predominantly monogenic disorders were identified and characterized, which led some investigators to speculate that individualized drug treatment was just around the corner. Informative DNA tests were sought to determine genetic predisposition to toxicity and cancer, thereby identifying individuals in which a drug was likely to be effective and those at increased risk of drug toxicity. These assays represent the leading edge of phenotype-genotype association studies, which are a major goal of clinical pharmacology and pharmacogenomics. Because of the complexity of the genome, however, the task is more challenging than anticipated originally. In the past decade we have come to appreciate how difficult it is to determine unequivocally either an exact phenotype or genotype. In the near future it seems unlikely that, by themselves, either transcriptomics or proteomics will be particularly helpful in achieving individualized drug therapy. However, recent advances in metabonomics are exciting and show promise. In the future, and perhaps in combination with proteomics, metabonomics might complement genomics in achieving personalized drug therapy.
在1930年至1990年间，几十种高外显率、主要为单基因的疾病被识别和表征，这使得一些研究人员推测个性化药物治疗已近在咫尺。人们寻求提供信息的DNA检测来确定对毒性和癌症的遗传易感性，从而识别出可能对某种药物有效的个体以及药物毒性风险增加的个体。这些检测代表了表型-基因型关联研究的前沿，而这是临床药理学和药物基因组学的一个主要目标。然而，由于基因组的复杂性，这项任务比最初预期的更具挑战性。在过去十年里，我们逐渐认识到明确确定精确的表型或基因型是多么困难。在不久的将来，转录组学或蛋白质组学自身似乎不太可能对实现个性化药物治疗有特别大的帮助。然而，代谢组学的最新进展令人兴奋且前景光明。未来，或许与蛋白质组学相结合，代谢组学可能在实现个性化药物治疗方面补充基因组学。
