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Oncotarget. 2016 Dec 13;7(50):82876-82888. doi: 10.18632/oncotarget.12657.

LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients.

Kim YJ1, Hong S2, Sung M1, Park MJ2, Jung K1,3, Noh KW1,3, Oh DY1,3, Lee MS1,3, Oh E1,3, Shin YK2,4, Choi YL1,3,5.

Author information

1
Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea.
3
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
4
The Center for Anti-cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, Korea.
5
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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.

KEYWORDS:

LYN; SRC; YES; dasatinib; lung adenocarcinoma subgroup

PMID:
27756880
PMCID:
PMC5347739
DOI:
10.18632/oncotarget.12657
[Indexed for MEDLINE]
Free PMC Article

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