Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer

• Published in: Oncotarget Vol. 7; no. 4; pp. 3884 - 3896
• Main Authors: Xu, Naiqing, Fang, Wenfeng, Mu, Libing, Tang, Yanna, Gao, Lei, Ren, Shengxiang, Cao, Dengfeng, Zhou, Lixin, Zhang, Aiqun, Liu, Deruo, Zhou, Caicun, Wong, Kwok-Kin, Yu, Lei, Zhang, Li, Chen, Liang
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 26.01.2016
• Subjects: Animals; Biomarkers, Tumor; Blotting, Western; Bronchi - drug effects; Bronchi - metabolism; Bronchi - pathology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cells, Cultured; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Genotype; Humans; Immunoenzyme Techniques; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mice; Mice, Transgenic; Mutation - genetics; Neoplasm Staging; NIH 3T3 Cells; Prognosis; Protein Kinase Inhibitors - pharmacology; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Research Paper; Survival Rate; lung cancer; tyrosine kinase inhibitor; transgenic mouse model; EGFR
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.6461

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.