A multistep validation process of biomarkers for preclinical drug development

被引:0
作者
W M Freeman
G V Bixler
R M Brucklacher
C-M Lin
K M Patel
H D VanGuilder
K F LaNoue
S R Kimball
A J Barber
D A Antonetti
T W Gardner
S K Bronson
机构
[1] Functional Genomics Core Facility,Department of Pharmacology
[2] Penn State College of Medicine,Department of Cellular & Molecular Physiology
[3] Penn State College of Medicine,Department of Ophthalmology
[4] Penn State College of Medicine,undefined
[5] Penn State College of Medicine,undefined
来源
The Pharmacogenomics Journal | 2010年 / 10卷
关键词
biomarker; drug development; preclinical; gene expression; diabetic retinopathy;
D O I
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中图分类号
学科分类号
摘要
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.
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页码:385 / 395
页数:10
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共 178 条
[11]  
Rolan P(1993)Successful anti-cancer drug targets able to pass FDA review demonstrate the identifiable signature distinct from the signatures of random genes and initially proposed targets N Engl J Med 329 977-986
[12]  
Atkinson AJ(2007)The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group JAMA 298 902-916
[13]  
Lesko LJ(2008)Management of diabetic retinopathy: a systematic review Invest Ophthalmol Vis Sci 49 479-489
[14]  
Lesko LJ(2007)Report from the NEI/FDA Ophthalmic Clinical Trial Design and Endpoints Symposium Nat Med 13 181-188
[15]  
Atkinson AJ(2006)Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation Curr Eye Res 31 231-240
[16]  
Gunther EC(2003)Differential expression of vitreous proteins in proliferative diabetic retinopathy Neurol Clin 21 709-728
[17]  
Stone DJ(2005)Visual dysfunction, neurodegenerative diseases, and aging Invest Ophthalmol Vis Sci 46 349-357
[18]  
Gerwien RW(2001)Expression of acute-phase response proteins in retinal Muller cells in diabetes Invest Ophthalmol Vis Sci 42 3047-3057
[19]  
Bento P(2008) retinal gene expression in early diabetes BMC Medical Genomics 1 26-674
[20]  
Heyes MP(2004)Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response Am J Ophthalmol 137 668-722