Gene Array and Fluorescence In situ Hybridization Biomarkers of Activity of Saracatinib (AZD0530), a Src Inhibitor, in a Preclinical Model of Colorectal Cancer
作者： John J. Arcaroli , Basel M. Touban , Aik Choon Tan , Marileila Varella-Garcia , Rebecca W. Powell
DOI: 10.1158/1078-0432.CCR-10-0066
关键词:
摘要: Purpose: To evaluate the efficacy of saracatinib (AZD0530), an oral Src inhibitor, in colorectal cancer (CRC) and to identify biomarkers that predict antitumor activity. Experimental Design: Twenty-three CRC cell lines were exposed saracatinib, baseline gene expression profiles three sensitive eight resistant vitro vivo used sensitivity independent group 10 human explant tumors using array K-Top Scoring Pairs ( K-TSP ) method. In addition, fluorescence situ hybridization (FISH) immunoblotting determined both copy number activation Src, respectively. Results: Two be saracatinib. The classifier (TOX>GLIS2, TSPAN7>BCAS4, PARD6G>NXN) achieved 70% (7 10) accuracy on test set. Evaluation by FISH showed a trend toward significance P = 0.066) with respect increase resistance Tumors FAK when compared tumors. Conclusions: Saracatinib significantly decreased tumor growth subset explants. A was predictive for increased pathway associated These results suggest FISH, classifier, have potential identifying patients would potentially benefit from treatment Clin Cancer Res; 16(16); 4165–77. ©2010 AACR.
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