title: LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients.
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.
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Sung
authors.affiliation: Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Jung
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Ka-Won
authors.initials: KW
authors.lastname: Noh
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Doo-Yi
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Ensel
authors.initials: E
authors.lastname: Oh
authors.affiliation: Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea.|The Center for Anti-cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.|Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000069439:Dasatinib / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D000069439:Dasatinib
keywords: LYN; SRC; YES; dasatinib; lung adenocarcinoma subgroup