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Predicting Sensitivity of Breast Tumors to Src-Targeted Therapies through Assessment of Cas/Src/BCAR3 Activity

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Rector and Visitors of the University of Virginia Charlottesville United States

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Purpose The purpose of this research is to assess the role of a signaling pathway comprised of the protein tyrosine kinase c-Src Src and two adaptor molecules, Cas and BCAR3, in promoting breast tumor growth, metastasis and therapeutic resistance toward Src-targeted small molecule inhibitors. Scope The proposed research employs 2- and 3-dimensional tissue culture models, transplantable mouse models of breast cancer, and analysis of human breast tumor samples. Major Findings Key results from the third year of support include 1 Further documentation using orthotopic tumor models demonstrating that BCAR3 is essential for tumor growth but that its interaction with Cas appears not to be required for this process 2 the development of a robust clonigenic assay that we have used to show that BCAR3 controls cell proliferationsurvival and dasatinib sensitivity and3 the acquisition of RNA-seq data that allow us to compare gene expression profiles as a function ofBCAR3 expression under 3 culture conditions plastic, 3D matrigel, and murine organoid cultures. The data we have generated are currently being prepared for publication we expect to submit the manuscript by the end of the year.

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Technical Report,15 Sep 2017,14 Sep 2018



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Approved For Public Release;

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