Research Papers:
LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients
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Yu Jin Kim1, Sungyoul Hong2, Minjung Sung1, Min Jeong Park2, Kyungsoo Jung1,3, Ka-Won Noh1,3, Doo-Yi Oh1,3, Mi-Sook Lee1,3, Ensel Oh1,3, Young Kee Shin2,4, Yoon-La Choi1,3,5
1Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea
3Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
4The Center for Anti-cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, Korea
5Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to:
Yoon-La Choi, email: [email protected]
Young Kee Shin, email: [email protected]
Keywords: LYN, dasatinib, lung adenocarcinoma subgroup, SRC, YES
Received: March 16, 2016 Accepted: October 01, 2016 Published: October 14, 2016
ABSTRACT
Therapies targeting SRC family kinases (SFKs) have shown efficacy in treating non-small cell lung cancer (NSCLC). However, recent clinical trials have found that the SFK inhibitor dasatinib is ineffective in some patient cohorts. Regardless, dasatinib treatment may benefit some NSCLC patient subgroups. Here, we investigated whether expression of LYN, a member of the SFK family, is associated with patient survival, the efficacy of dasatinib, and/or NSCLC cell viability. LYN expression was associated with poor overall survival in a multivariate analysis, and this association was strongest in non-smoker female patients with adenocarcinoma (ADC). In lung ADC cells, LYN expression enhanced cell proliferation, migration, and invasion. Dasatinib inhibited LYN activity and decreased cell viability in LYN-positive ADC cell lines and xenografts. Additionally, we identified the SFKs SRC and YES as candidate dasatinib targets in LYN-negative ADC cell lines. Our findings suggest that LYN is a useful prognostic marker and a selective target of dasatinib therapy in the lung ADC subpopulation especially in female non-smokers with lung ADC.