Abstract 3457: Galectin-1 suppression enhances combined anti-EGFR and radiation-therapy of NSCLC

Abstract

Abstract Lung cancer remains the leading cause of cancer related death worldwide and will account for nearly 160,000 deaths in the United States alone in 2010. Between 80-90% of all cases diagnosed are classified as non-small cell lung cancer (NSCLC). Recent studies have shown a significant subpopulation of patients diagnosed with NSCLC have an activation of the epidermal growth factor receptor (EGFR) domain resulting from gene amplification, overexpression, or kinse-domain activating mutations. EGFR inhibitors such as Erlotinib and Gefitnib have shown promising results in this subpopulation of patients however median overall survival remains poor. LSGAL1, Galectin-1 (GAL1), is a beta-galactoside-binding protein we recently identified to play an important role in the activation of the PI3-Kinase pathway located directly downstream of EGFR. Silencing Galectin-1 in combination with an EGFR-inhibitor and radiation therapy may be a promising therapeutic strategy for patients with NSCLC. Using a short-hairpin RNA strategy we silenced GAL1 expression in four different NCSLC cell lines and assessed their relative radioresistance via clonogenic survival assay in the presence and absence of an EGFR inhibitor. In order to elucidate the mechanism between GAL1 and EGFR, western blotting and QPRC analysis was performed on downstream pathway members, specifically the RAS/PI3-Kinase and RAS/ERK signaling cascades. Functional assays focusing on proliferation/survival were carried out to determine the effect silencing GAL1 had on the combination of EGFR inhibition and radiation therapy in our NSCLC cell lines. Our preliminary results suggest silencing GAL1 reduces the clonogenic survival of NSCLC cells when used in combination with an EGFR inhibitor following irradiation. In addition well known players within PI3-Kinase pathway such as pAKT S473 appear to be altered in the absence of GAL1. Our preliminary findings suggest GAL1 is a promising therapeutic target in NSCLC when used in combination with an EGFR inhibitor and radiation therapy and is worthy of further investigation. 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 3457. doi:1538-7445.AM2012-3457