Abstract LB-067: Proteomic analysis identifies multi-dimensional deregulated signaling pathways in SCLC lung cancer

Abstract

Abstract Lung cancer is the most common type of cancer in the U.S., with 5 yr. survival rates of 18% and 6% for non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) patients, respectively. In spite of success with targeted therapies for 15-20% of patients with NSCLCs, the success is generally short-lived as the tumors become resistant to treatment. In contrast to NSCLC, no successful targeted therapies have been identified in SCLC. Further understanding of the regulatory cell signaling networks for SCLCs, may enable the discovery of new actionable lung cancer drivers. Posttranslational modifications (PTMs), including phosphorylation, acetylation and methylation, act alone and in combination to regulate protein function, cellular behavior and epigenetics. All three types of PTMs are deregulated in various cancers. In this study we developed a highly quantitative MS/MS approach combining TMT labeling with a number of motif and site-specific antibodies to identify deregulated signaling pathways between tumor and normal specimens. PTM-specific antibodies were used to enrich modified peptides followed by 6-plex TMT mass-spec analyses to quantitatively measure over 15,300 differentially phosphorylated, acetylated, and methylated sites on over 4,600 proteins from 17 SCLC patient tissues and 5 para-normals. Understanding cell-signaling networks at the intersection of multiple pathways and protein modification systems in SCLC lung cancers leads to the identification of new druggable disease drivers. Citation Format: Klarisa Rikova, Ben Hall, Tyler Levy, Anthony Possemato, Mike Aguiar, Sean Beausoleil, Jian Min Ren, Kimberly Lee Lee, Scott Lonning, Michael Comb. Proteomic analysis identifies multi-dimensional deregulated signaling pathways in SCLC lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-067.