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LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients
Yu Jin Kim1, Sungyoul Hong2, Minjung Sung1
1Laboratory of Cancer Genomics and Molecular Pathology, 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.
Insights
LYN, a SRC family kinase, is linked to poorer survival in non-small cell lung cancer (NSCLC), particularly in female non-smokers with adenocarcinoma. Dasatinib effectively targets LYN-positive NSCLC, suggesting LYN as a prognostic marker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) therapies targeting SRC family kinases (SFKs) show promise.
- However, dasatinib, an SFK inhibitor, has variable efficacy in NSCLC patients.
- Identifying predictive biomarkers for dasatinib response is crucial.
Purpose of the Study:
- To investigate the prognostic role of LYN, an SFK member, in NSCLC patient survival.
- To determine the association between LYN expression and dasatinib efficacy.
- To evaluate LYN's impact on NSCLC cell behavior and viability.
Main Methods:
- Multivariate analysis of LYN expression and patient survival data.
- In vitro studies assessing LYN's effect on lung adenocarcinoma (ADC) cell proliferation, migration, and invasion.
- In vitro and in vivo experiments evaluating dasatinib's efficacy in LYN-positive and LYN-negative ADC models.
Main Results:
- LYN expression correlated with poor overall survival in NSCLC, especially in female non-smokers with ADC.
- LYN enhanced proliferation, migration, and invasion in lung ADC cells.
- Dasatinib inhibited LYN activity, reduced cell viability in LYN-positive ADC cells and xenografts, and identified SRC and YES as targets in LYN-negative cells.
Conclusions:
- LYN serves as a prognostic biomarker for NSCLC patient survival.
- LYN is a selective therapeutic target for dasatinib in a specific NSCLC subpopulation (female non-smokers with ADC).
- Further research into SFK signaling pathways can optimize targeted therapies for NSCLC.
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