Abstract 5270: The role of EphA2 in the maintenance of cell viability of KRAS mutant non-small cell lung cancer.

Abstract

Abstract Lung cancer is the leading cause of cancer-related deaths in the United States. Non-small cell lung cancer (NSCLC) is the most common histological subtype of lung cancer, which can be further subdivided based on its unique profile of oncogenic mutations. Identifying molecular subtypes of NSCLC and matching patients with appropriate targeted therapies is critically important for the treatment of this disease. Although significant progress has been made to develop novel, molecularly-targeted therapeutics, challenges still remain in targeting commonly occurring mutations in NSCLC, such as those in KRAS. Overcoming these challenges will require astute strategies to identify and inhibit novel kinase targets required for cell viability in these subtypes of lung cancer. To this end, we have shown that the EphA2 receptor tyrosine kinase plays a unique role in the maintenance of cell viability in NSCLC, especially those with KRAS mutations. EphA2 is generally overexpressed in NSCLC and even further overexpressed in KRAS mutant NSCLC. Preliminary data from our lab has shown that knockdown of EphA2 expression in a large number of human NSCLC cell lines dramatically inhibits cell viability in cell lines bearing KRAS mutations. To further understand this phenotype, we are working to define the molecular mechanisms downstream of EphA2 that are critical for cell viability in this genotype and to model the effects EphA2 deficiency in vivo using transgenic mouse models. Based on our preliminary data, we propose that EphA2 provides a novel target for modulating cell viability in lung cancers with KRAS mutations associated with limited therapeutic options. Citation Format: Katherine R. Amato, Jin Chen. The role of EphA2 in the maintenance of cell viability of KRAS mutant non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5270. doi:10.1158/1538-7445.AM2013-5270