Transcriptomics,Multiomics

Dataset Information

39

Transcription profiling of human peripheral blood mononuclear cells treated with a CDK inhibitor


ABSTRACT: A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis. Experiment Overall Design: 40 samples were initially run, 37 passed QC and were analyzed, samples were run in 6 independent replicates and were treated with either vehicle, R547 at the IC90, or R547 at 3 times the IC90. Additionally, untreated time zero samples were analyzed as a further control

REANALYSED by: E-GEOD-15389

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: James Rosinski   

PROVIDER: E-GEOD-15389 | ArrayExpress | 2015-09-02

SECONDARY ACCESSION(S): GSE15389PRJNA122945

REPOSITORIES: GEO, ArrayExpress

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Publications

Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.

Berkofsky-Fessler Windy W   Nguyen Tri Q TQ   Delmar Paul P   Molnos Juliette J   Kanwal Charu C   DePinto Wanda W   Rosinski James J   McLoughlin Patricia P   Ritland Steve S   DeMario Mark M   Tobon Krishna K   Reidhaar-Olson John F JF   Rueger Ruediger R   Hilton Holly H  

Molecular cancer therapeutics 20090915 9


A genomics-based approach to identify pharmacodynamic biomarkers was used for a cyclin-dependent kinase inhibitory drug. R547 is a potent cyclin-dependent kinase inhibitor with a potent antiproliferative effect at pharmacologically relevant doses and is currently in phase I clinical trials. Using preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on  ...[more]

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