title: Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer.
abstract: Current guidelines for lung cancer treatment with EGFR tyrosine kinase inhibitors (TKI) include only patients with mutated EGFR, although some patients with wildtype EGFR (wt-EGFR) have exhibited positive responses to this therapy as well. Biomarkers predicting the benefit from EGFR-TKIs treatment remain to be determined for patients with wild-type EGFR.Here, we report that wt-EGFR overexpression transformed cells in vitro and induced tumorigenesis in vivo in transgenic mouse models. Wt-EGFR driven lung cancer was hypersensitive to TKI treatment in mouse model. Lung cancer patients with high-expression of wt-EGFR showed longer Overall Survival in comparison to low-expression patients after TKI treatment. Our data therefore suggest that treatment with EGFR inhibitors should be extended to include not only patients with mutated EGFR but also a subset of patients with overexpression of wt-EGFR.
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.|National Institute of Biological Sciences, Beijing, Beijing, China.|Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Naiqing
authors.initials: N
authors.lastname: Xu
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: Tsinghua University School of Medicine, Beijing, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Mu
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Tang
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Shanghai Pulmonary Hospital, Shanghai, China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cao
authors.affiliation: Peking University Cancer Hospital, Beijing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: General Hospital of People's Liberation Army, Beijing, China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Deruo
authors.initials: D
authors.lastname: Liu
authors.affiliation: Shanghai Pulmonary Hospital, Shanghai, China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.|National Institute of Biological Sciences, Beijing, Beijing, China.|Chinese Academy of Medical Sciences, Beijing, China.|National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D041681:NIH 3T3 Cells; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; lung cancer; transgenic mouse model; tyrosine kinase inhibitor