Abstract
Lung cancers are the leading cause of cancer deaths globally. In particular, non-small cell lung cancer (NSCLC) is a devastating disease, and is rarely curable. Hyperactivation of mitogenic signaling cascades is a hallmark of cancer development, including for lung cancers. Targeted therapies inhibiting specific receptor tyrosine kinases have shown clinical promise, but rarely produce complete responses and are not curative, suggesting the existence of escape mechanisms promoting cell survival. Using a loss-of-function, whole genome shRNA screen, we identified various components and mediators of the canonical Wnt pathway that contribute to the maintenance of NSCLC cells during inhibition of the epidermal growth factor receptor (EGFR). Modulation of tankyrases, casein kinases and different components of the Wnt pathway with shRNAs or small molecules, in vitro and in vivo, significantly increased the efficacy of EGFR inhibitors, thus revealing a critical role for the canonical Wnt pathway in maintaining lung cancer cells during EGFR inhibition. Targeting the Wnt/β-catenin pathway together with EGFR inhibition in the clinic could lead to more durable remissions for non-small cell lung cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5135. doi:1538-7445.AM2012-5135
