Program in Pharmacogenomics, College of Medicine, The Ohio State University, Columbus, OH 43210-1239, USA.
Int J Pharm. 2011 Aug 30;415(1-2):2-4. doi: 10.1016/j.ijpharm.2011.04.048. Epub 2011 Apr 23.
The role of genomics in personalized medicine continues to undergo profound changes, in step with dramatic technological advances. Ability to sequence the entire human genome with relative ease raises expectations that we can use an individual's complete genomic blueprint to understand disease risk and predicting therapy outcomes, thereby, optimizing drug therapy. Yet, doubts persist as to what extent genetic/genomic factors influence disease and treatment outcomes or whether robust predictive biomarker tests can be developed. Encompassing more than just DNA sequences, the definition of genomics now often is taken to include transcriptomics, proteomics, metabolomics, and epigenomics, with integration of genomic and environmental factors, in an area referred to systems biology. While we can learn much about a cell's innermost workings, summation of these diverse areas is far from enabling the prediction of therapeutic outcomes. Typically, only a handful of specific biomarkers, genetic or otherwise, are 'actionable', i.e., they can be used to guide therapy. I will focus on pharmacogenetic biomarkers, highlighting current successes but also the main challenges that remain in optimizing individualized therapy.
基因组学在个性化医学中的作用随着技术的巨大进步而不断发生深刻的变化。能够相对轻松地对整个人类基因组进行测序，这使得人们期望能够利用个体的完整基因组蓝图来了解疾病风险和预测治疗效果，从而优化药物治疗。然而，人们仍然怀疑遗传/基因组因素在多大程度上影响疾病和治疗效果，或者是否可以开发出可靠的预测生物标志物测试。现在，基因组学的定义不仅包括 DNA 序列，还通常包括转录组学、蛋白质组学、代谢组学和表观基因组学，以及基因组和环境因素的整合，这在系统生物学领域中有所体现。虽然我们可以深入了解细胞的内部运作，但将这些不同领域综合起来，还远远不能实现治疗效果的预测。通常，只有少数特定的生物标志物（遗传的或其他的）是“可操作的”，也就是说，它们可以用于指导治疗。我将重点关注药物遗传学生物标志物，突出当前的成功案例，但也强调在优化个体化治疗方面仍然存在的主要挑战。
