A multistep validation process of biomarkers for preclinical drug development
A multistep validation process of biomarkers for preclinical drug development
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DOI：
10.1038/tpj.2009.60
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发表时间：
2010-10-01
影响因子：
2.8
通讯作者：
Bronson, S. K.
中科院分区：
文献类型：
--
作者：
Freeman, W. M.;Bixler, G. V.;Bronson, S. K.
可以在临床前模型中以高通量、可重复的方式测量的生物标志物提供了提高药物开发速度和功效的潜力。用于许多病症的治疗剂的开发受到可用于测量药效和疾病进展的有限数量的经验证的临床前生物标志物的阻碍，但是临床前生物标志物的验证过程受到的关注有限。本报告定义了一个五步临床前生物标志物验证过程，并将该过程应用于糖尿病视网膜病变的病例研究。通过显示基因表达组是高度可再现的，与疾病表现一致，准确地对个体动物进行分类并鉴定用已知治疗剂治疗的动物，可以认为生物标志物组是有效的。由14个基因（C1 inh、C1 s、Carhsp 1、Chi 3l 1、Gat 3、Gbp 2、Hspb 1、Icam 1、Jak 3、Kcne 2、Lama 5、Lgals 3、Nppa、Timp 1）组成的特定生物标志物组可用于糖尿病视网膜病变药理学研究，此处概述的生物标志物开发过程适用于其他疾病的药物开发工作。The Pharmacogenomics Journal（2010）10，385-395; doi：10.1038/tpj.2009.60; 2009年12月8日在线发表
Biomarkers that can be measured in preclinical models in a high-throughput, reproducible manner offer the potential to increase the speed and efficacy of drug development. Development of therapeutic agents for many conditions is hampered by the limited number of validated preclinical biomarkers available to gauge pharmacoefficacy and disease progression, but the validation process for preclinical biomarkers has received limited attention. This report defines a five-step preclinical biomarker validation process and applies the process to a case study of diabetic retinopathy. By showing that a gene expression panel is highly reproducible, coincides with disease manifestation, accurately classifies individual animals and identifies animals treated with a known therapeutic agent, a biomarker panel can be considered validated. This particular biomarker panel consisting of 14 genes (C1inh, C1s, Carhsp1, Chi3l1, Gat3, Gbp2, Hspb1, Icam1, Jak3, Kcne2, Lama5, Lgals3, Nppa, Timp1) can be used in diabetic retinopathy pharmacotherapeutic research, and the biomarker development process outlined here is applicable to drug development efforts for other diseases. The Pharmacogenomics Journal (2010) 10, 385-395; doi:10.1038/tpj.2009.60; published online 8 December 2009