Date of Award

2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmacology and Experimental Therapeutics

Abstract

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 mutant NSCLC cells promotes EGFR TKI resistance and EMT. CXCR7 knockdown restores sensitivity to EGFR TKI and partially reverse EMT. In summary, our data suggested CXCR7 as a promising therapeutic target for preventing or overcoming EGFR TKI resistance in a subset of EGFR mutant NSCLC patients.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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