A multistep validation process of biomarkers for preclinical drug development

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)385-395
Number of pages11
JournalPharmacogenomics Journal
Volume10
Issue number5
DOIs
StatePublished - Oct 1 2010

Fingerprint

Biomarkers
Pharmaceutical Preparations
Diabetic Retinopathy
Disease Progression
Gene Expression
Therapeutics
Research
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Freeman, W. M., Bixler, G. V., Brucklacher, R. M., Lin, C. M., Patel, K. M., Vanguilder, H. D., ... Bronson, S. K. (2010). A multistep validation process of biomarkers for preclinical drug development. Pharmacogenomics Journal, 10(5), 385-395. https://doi.org/10.1038/tpj.2009.60
Freeman, W. M. ; Bixler, G. V. ; Brucklacher, R. M. ; Lin, C. M. ; Patel, K. M. ; Vanguilder, H. D. ; Lanoue, K. F. ; Kimball, S. R. ; Barber, A. J. ; Antonetti, D. A. ; Gardner, T. W. ; Bronson, S. K. / A multistep validation process of biomarkers for preclinical drug development. In: Pharmacogenomics Journal. 2010 ; Vol. 10, No. 5. pp. 385-395.
@article{f4412fe3bc1b492bb6bfb4fb96873d56,
title = "A multistep validation process of biomarkers for preclinical drug development",
abstract = "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.",
author = "Freeman, {W. M.} and Bixler, {G. V.} and Brucklacher, {R. M.} and Lin, {C. M.} and Patel, {K. M.} and Vanguilder, {H. D.} and Lanoue, {K. F.} and Kimball, {S. R.} and Barber, {A. J.} and Antonetti, {D. A.} and Gardner, {T. W.} and Bronson, {S. K.}",
year = "2010",
month = "10",
day = "1",
doi = "10.1038/tpj.2009.60",
language = "English (US)",
volume = "10",
pages = "385--395",
journal = "Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
number = "5",

}

Freeman, WM, Bixler, GV, Brucklacher, RM, Lin, CM, Patel, KM, Vanguilder, HD, Lanoue, KF, Kimball, SR, Barber, AJ, Antonetti, DA, Gardner, TW & Bronson, SK 2010, 'A multistep validation process of biomarkers for preclinical drug development', Pharmacogenomics Journal, vol. 10, no. 5, pp. 385-395. https://doi.org/10.1038/tpj.2009.60

A multistep validation process of biomarkers for preclinical drug development. / Freeman, W. M.; Bixler, G. V.; Brucklacher, R. M.; Lin, C. M.; Patel, K. M.; Vanguilder, H. D.; Lanoue, K. F.; Kimball, S. R.; Barber, A. J.; Antonetti, D. A.; Gardner, T. W.; Bronson, S. K.

In: Pharmacogenomics Journal, Vol. 10, No. 5, 01.10.2010, p. 385-395.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multistep validation process of biomarkers for preclinical drug development

AU - Freeman, W. M.

AU - Bixler, G. V.

AU - Brucklacher, R. M.

AU - Lin, C. M.

AU - Patel, K. M.

AU - Vanguilder, H. D.

AU - Lanoue, K. F.

AU - Kimball, S. R.

AU - Barber, A. J.

AU - Antonetti, D. A.

AU - Gardner, T. W.

AU - Bronson, S. K.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77957154265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957154265&partnerID=8YFLogxK

U2 - 10.1038/tpj.2009.60

DO - 10.1038/tpj.2009.60

M3 - Article

C2 - 19997081

AN - SCOPUS:77957154265

VL - 10

SP - 385

EP - 395

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

SN - 1470-269X

IS - 5

ER -

Freeman WM, Bixler GV, Brucklacher RM, Lin CM, Patel KM, Vanguilder HD et al. A multistep validation process of biomarkers for preclinical drug development. Pharmacogenomics Journal. 2010 Oct 1;10(5):385-395. https://doi.org/10.1038/tpj.2009.60