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Pharmacy and Pharmaceutical Sciences

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Loyola University Chicago

Master's Theses

2014

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Identifying Oncogenic Drivers In Nsclc Cells Harboring Egfr Kinase Domain Mutation With Resistance To Egfr Tki And Mesenchymal Phenotype, Yandi Gao Jan 2014

Identifying Oncogenic Drivers In Nsclc Cells Harboring Egfr Kinase Domain Mutation With Resistance To Egfr Tki And Mesenchymal Phenotype, Yandi Gao

Master's Theses

EGFR kinase domain mutant NSCLC cells are exquisitely dependent on mutant EGFR for cell survival and proliferation. Patients with mutant EGFR respond well to the EGFR inhibitors. However, acquired drug resistance greatly limits the efficacy of the treatment. About 15% of the resistant tumors present an evidence of epithelial to mesenchymal transition (EMT). We hypothesize that the induction of mesenchymal promotes aberrant upregulation of other oncogenic drivers to replace the oncogenic mutant EGFR.

We observed overexpression of CXCR7 in NSCLC models of acquired resistance to EGFR TKI with mesenchymal phenotype. Additionally, our studies demonstrate that ectopically overexpressing CXCR7 in EGFR …