Identification Of A Novel Therapeutic Target In Lung Adenocarcinoma

The reactivation of biologic signaling events that occur throughout fetal development has been observed during malignant cell transformation and tumor progression. Transcription factors are typically at the hub of these signaling events, such as NKX2-1 and several ETS transcription factors. ELF3 is an uncharacterized ETS family member that is highly expressed during fetal lung development and could play a biologic role in lung cancer based on its location within the recurrently gained chromosome 1q. We hypothesize that ELF3 is a novel oncogenic transcription factor and a therapeutic target. Multiple independent datasets encompassing 1,685 clinical samples of lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), small cell lung cancer, and nonmalignant lung tissues were analyzed to establish the frequency of ELF3 overexpression and underlying genetic mechanisms of selection. ELF3 overexpression was validated by immunohistochemistry. Associations with patient survival were tested using the log-rank method. Isogenic cell lines were established to assess oncogenic phenotypes including tumor growth in a xenograft model. Protein-protein interaction (PPI) networks were constructed around ELF3, and integrated pathway analysis was performed to decipher the signaling network disruptions resulting from ELF3 overexpression. ELF3 overexpression was frequently observed in LUAD (u003e2-fold: BCCA 73% TCGA 40%), but was not observed in other lung cancer subtypes. Similarly, high ELF3 expression was significantly associated with poor overall survival of LUAD patients (p We have deciphered the oncogenic role of ELF3 in LUAD. Its requirement for tumor growth in our model indicates that therapeutic targeting of ELF3 could benefit the 73% of patients who display ELF3 overexpression. Citation Format: Katey S.S. Enfield, Erin A. Marshall, Christine Anderson, Kevin W. Ng, Sara Rahmati, Zhaolin Xu, Calum E. MacAulay, Stephen Lam, William W. Lockwood, Raj Chari, Aly Karsan, Igor Jurisica, Wan L. Lam. Identification of a novel therapeutic target in lung adenocarcinoma [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A26.