Cyclooxygenase-2 contributes to mutant epidermal growth factor receptor lung tumorigenesis by promoting an immunosuppressive environment

Abstract

Targeted therapies reduce growth of mutant epidermal growth factor receptor (EGFR) non-small cell lung cancers, but most patients develop drug resistance. This has led to efforts to develop additional therapies. We found abundant activation of the cyclooxygenase-2 (COX-2) axis in a mouse model of mutant EGFR lung cancer. Inhibiting COX-2 in the mice significantly reduced lung tumor growth, and dual targeting of COX-2 and EGFR had more pronounced effects. Collectively, our data and published data have led us to hypothesize that COX-2 contributes to mutant EGFR lung tumorigenesis, in part, by promoting an immunosuppressive environment that facilitates tumor progression.