药物表型组学:药理毒理学和个体化医学的新模式(英文)  

Pharmacophenomics: a new paradigm for pharmacology, toxicology,and personalized medicine

作　　者：Dayue Darrel DUAN 韩业山[2] 李立[2] 赵建中[3] 王忠[4] 

机构地区：[1]Laboratory of Cardiovascular Phenomics,Department of Pharmacology,University of Nevada School of Medicine,1664 N Virginia Street,MS 318,Reno,NV,89557 [2]常州市第二人民医院麻醉科,江苏常州213003 [3]常州市第二人民医院心脏内科,江苏常州213003 [4]中国中医科学院临床医学基础研究所,北京100700

出　　处：《中国药理学与毒理学杂志》2014年第1期1-9,共9页Chinese Journal of Pharmacology and Toxicology

基　　金：Cardiovascular Phenomics in the Center for Molecular Medicine and Department of Pharmacology,School of Medicine at University of Nevada is supported by NIH grants#HL63914,#HL106252,and#HL113598~~

摘　　要：近年来,药物基因组学(pharmacogenomics)研究收集了大量有关遗传多态性对药物反应(疗效和毒性反应)的普遍影响的信息,并突出显示了基因组指导下的个体化药物治疗的必要性。然而,由于疾病和药物治疗临床效果和毒性反应的内在复杂性,并且往往涉及数十个或数百个基因和环境因素的动态变化的影响,将药物基因组学的知识转化为个体化医学的临床实践面临着重大的挑战和障碍。为了克服这些障碍,些包括药物蛋白质组学(pharmacoproteomics)和药物代谢组学(pharmacometabolomics)等在内的新学科应运而生。同时,这些"组学"研究也揭示了在越来越详细的基因组/蛋白质组学/代谢组学的变异性与目前定义的各种临床疾病和药物治疗表型的复杂性之间存在着种非平行关系。因而要种新的研究模式来重新定义这种表型与基因组/蛋白质组/代谢组之间的非平行关系。此文将介绍个跨领域的新学科,它能为从只注重于单纯的表型-基因型关系的研究模式转化到系统性的表型组-基因组关系的研究方法提供整套新的技术平台,从而在系统生物学水平重新定义具有整合性的药物治疗靶点群,改进药物研究的模式,使其更适合于临床个体化医学与药物治疗。这个新学科就是"药物表型组学(pharmacophenomics)"。表型组(phenome)是在特定环境影响下有机体基因组/蛋白质组/代谢组表达的整体表型特征的总和。表型组学(phenomics)则是对表型组与基因组/转录组(transcritome)/蛋白质组/代谢组/相互作用组(interactome)和环境因素变化之间的复杂关系的定量研究。药物表型组学将系统性地确定对应于定义明确的疾病表型组的综合性药物靶标群。因此,药物表型组学将与药物基因组学、药物蛋白质组学组学和药物代谢组学等学科互补,为药物作用和毒性的研究提供个革命性的新模式。The extensive pharmacogenomic studies have documented pervasive effects of genetic polymorphisms on drug responses（ efficacy and toxicity） and highlighted the necessity for the genomically-guided personalized drug therapy. Translation of the knowledge of pharmacogenomics into the clinical practice of personalized medicine,however,has become a major challenge due to the intrinsic complexity of the targeted disease and the outcomes of drug treatment,which often involve dynamic alternations in tens or hundreds of genes and environmental factors. To overcome these challenges newer transdisciplines including pharmacoproteomics and pharmacometabolomics were developed. These ＇omics＇ studies have also revealed the increasingly detailed genomic /proteomic /metabolomic variations do not have a parallel relation with the complex clinical phenotype of disease and drug therapy. Clearly, newer approaches to redefine this relationship is needed. Here,we introduce a new transdiscipline termed ″ pharmacophenomics″ that will offer a suite of new technologies and platforms for the transition from focused phenotype-genotype study to a systematic phenomegenome approach and refine drug research with systematically-defined drug response and therapeutic targets suitable for personalized medicine. A phenome is the sum total of an organism＇s phenotypic traits that signify the expression of genome /proteome /metabolome under specific environmental influence. Phenomics is the study of phenome to quantitatively correlate complex traits to variability in genome / transcritome /proteome /interactome /metabolome and environmental factors. With well-defined disease phenome pharmacophenomics will identify the corresponding therapeutic targets and drug responses at the level of systems biology. As a complement of pharmacogenomics,pharmacoproteomics,and pharmacometabolomics,pharmacophenomics will provide a new paradigm for the study of drug effects and toxicities.

关 键 词：药物基因组学 药物代谢组学 表型组 表型组学 个体化医学 

分 类 号：R96[医药卫生—药理学] R99[医药卫生—药学]