Abstract A01: The role of EphA2 in KRAS mutant non-small cell lung cancer

Abstract

Abstract Lung cancer is the leading cause of cancer-related deaths in the United States accounting for approximately 160,000 deaths per year. Emerging data from sequencing efforts has emphasized the importance of identifying molecular subtypes of non-small cell lung cancer (NSCLC) and matching patients with appropriate targeted therapies for the most effective 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 KRAS. Overcoming these challenges will require strategies to identify and inhibit novel targets required for the suppression of 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 activating KRAS mutations. EphA2 is generally overexpressed in NSCLC and even further overexpressed in KRAS mutant NSCLC. Preliminary data from our lab has shown that silencing of EphA2 expression dramatically inhibits cell viability in human NSCLC cell lines bearing KRAS mutations. To further understand this phenotype, we are working to define the molecular mechanism downstream of EphA2 that is critical for maintaining cell viability in KRAS mutant NSCLC. Additionally, we have created a transgenic mouse model of KRAS mutant NSCLC with EphA2 depletion to study the role of EphA2 in KRAS driven lung tumorigenesis . Based on our preliminary data, we propose that EphA2 provides a novel target for modulating cell viability in lung cancers with KRAS mutations which are currently associated with limited therapeutic options. Citation Format: Katherine Amato, Shan Wang, Andrew Hastings, Haiying Chen, Daniel Colvin, Fei Ye, Jin Chen. The role of EphA2 in KRAS mutant non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr A01. doi: 10.1158/1557-3125.RASONC14-A01