Unknown,Transcriptomics,Genomics,Proteomics

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Genes regulated by PCK Inhibitors, enzastaurin and Go, in CAL-27 cells, a SCCHN cell line


ABSTRACT: Efficacy of the Multi-Kinase Inhibitor Enzastaurin is Dependent on Cellular Signaling Context Testing a panel of SCCHN cell lines revealed variable sensitivity to enzastaurin which correlated significantly with baseline cyclin D1 protein expression. Moreover, sensitivity and resistance could be reversed, respectively, by expression or depletion of cyclin D1. Furthermore, analysis of sensitive and resistant cell lines revealed distinct differences in cyclin D1 regulation. Enzastaurin modulated cyclin D1 synthesis via an AKT regulated pathway in the former while high level CCND1 gene amplification was present in the latter. These results underscore the critical relevance of cellular signaling context in developing cancer therapies, in general, and suggest that enzastaurin, in particular, would be most effective in tumors where baseline cyclin D1 expression is low to moderate and physiologically regulated. CAL-27 cells were treated with the inhibitors for 24 hours and the gene expression from each group were analyzed

ORGANISM(S): Homo sapiens

SUBMITTER: Wen Kuo 

PROVIDER: E-GEOD-22811 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Efficacy of the multi-kinase inhibitor enzastaurin is dependent on cellular signaling context.

Kuo Wen-Liang WL   Liu Jing J   Mauceri Helena H   Vokes Everett E EE   Weichselbaum Ralph R   Rosner Marsha Rich MR   Cohen Ezra Eddy Wyssam EE  

Molecular cancer therapeutics 20100928 10


The number of targeted small molecules being developed in oncology is increasing rapidly. Many of these are designed to inhibit multiple kinases, and thus the mechanisms of responsiveness and predictive biomarkers can be difficult to discern. In fact, with few exceptions, multi-kinase inhibitors are developed with limited mechanism-based patient selection. Enzastaurin is a multi-kinase inhibitor being studied in several malignancies that we hypothesized would be active in squamous cell carcinoma  ...[more]

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