TY - JOUR
T1 - Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients
AU - Berkofsky-Fessler, Windy
AU - Nguyen, Tri Q.
AU - Delmar, Paul
AU - Molnos, Juliette
AU - Kanwal, Charu
AU - DePinto, Wanda
AU - Rosinski, James
AU - McLoughlin, Patricia
AU - Ritland, Steve
AU - DeMario, Mark
AU - Tobon, Krishna
AU - Reidhaar-Olson, John F.
AU - Rueger, Ruediger
AU - Hilton, Holly
PY - 2009/9/1
Y1 - 2009/9/1
N2 - 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 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. Based on the results, eight genes (FLJ44342, CD86, EGR1, MKI67, CCNB1, JUN, HEXIM1, and PFAAP5) were selected as dose-responsive pharmacodynamic biomarkers for phase II clinical trials.
AB - 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 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. Based on the results, eight genes (FLJ44342, CD86, EGR1, MKI67, CCNB1, JUN, HEXIM1, and PFAAP5) were selected as dose-responsive pharmacodynamic biomarkers for phase II clinical trials.
UR - http://www.scopus.com/inward/record.url?scp=70349499021&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349499021&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-09-0083
DO - 10.1158/1535-7163.MCT-09-0083
M3 - Article
C2 - 19755512
AN - SCOPUS:70349499021
SN - 1535-7163
VL - 8
SP - 2517
EP - 2525
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
IS - 9
ER -
