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

// Naiqing Xu 1,2,3,* , Wenfeng Fang 4,* , Libing Mu 5 , Yanna Tang 4 , Lei Gao 2 , Shengxiang Ren 6 , Dengfeng Cao 7 , Lixin Zhou 8 , Aiqun Zhang 9 , Deruo Liu 10 , Caicun Zhou 6 , Kwok-Kin Wong 11 , Lei Yu 12 , Li Zhang 4 and Liang Chen 1,2,3,13 1 Graduate School of Peking Union Medical College, Beijing, China 2 National Institute of Biological Sciences, Beijing, Beijing, China 3 Chinese Academy of Medical Sciences, Beijing, China 4 Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, P. R. China 5 Tsinghua University School of Medicine, Beijing, China 6 Shanghai Pulmonary Hospital, Shanghai, China 7 Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing, China 8 Peking University Cancer Hospital, Beijing, China 9 General Hospital of People’s Liberation Army, Beijing, China 10 Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China 11 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 12 Beijing Tongren Hospital, Capital Medical University, Beijing, China 13 National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, China * These author have contributed equally to this work Correspondence to: Liang Chen, email: // Li Zhang, email: // Keywords : EGFR, transgenic mouse model, tyrosine kinase inhibitor, lung cancer Received : April 22, 2015 Accepted : November 15, 2015 Published : December 04, 2015 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.