Abstract 2785: LYN is a new prognostic and therapeutic target in non-small cell lung cancer

Abstract

Abstract SRC family kinases (SFKs) have a strong rationale as a clinical strategy in non-small cell lung cancer (NSCLC). Unfortunately, the reviewed study showed disappointing activity of SFK inhibitor dasatinib in molecularly unselected patient cohort. Therefore, the studies in NSCLC should be investigated to identify patients more likely to benefit from dasatinib either as monotherapy or in combination with other agents. Here, we considered that LYN may play specific roles in lung cancer and therefore analysed survival prognosis according to the expression of LYN and the effect of dasatinib on the inhibition of cell growth and LYN activity. We evaluated LYN expression by immunohistochemistry on 446 NSCLCs using paraffin-embedded tissues. Elevated LYN expression level of NSCLCs, especially in adenocarcinoma, female, and non-smoker, affected poor overall survival (OS, P=0.036). In lung adenocarcinoma cell lines, LYN expression impacted on cell proliferation, migration and invasion. Dasatinib treatment resulted in decreased cell viability in most of these cell lines. Also, we found that dasatinib suppressed active tyrosine phosphorylation of LYN. In the resistant cell lines, H23 and SK-LU-1, which showed elevated epidermal growth factor (EGFR) and MET activities, combined treatment of EGFR or MET inhibitor with dasatinib revealed the synergistic effects on decreased cell viability. Our findings highly suggest that LYN has potential as a new selected target molecule of SFKs in the treatment of NSCLCs. Citation Format: Yu Jin Kim, Minjung Sung, Min Jeong Park, Young Kee Shin, Yoon-La Choi. LYN is a new prognostic and therapeutic target in non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2785. doi:10.1158/1538-7445.AM2014-2785