Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer
Metrics: PDF 2519 views | HTML 1785 views | ?
Naiqing Xu1,2,3,*, Wenfeng Fang4,*, Libing Mu5, Yanna Tang4, Lei Gao2, Shengxiang Ren6, Dengfeng Cao7, Lixin Zhou8, Aiqun Zhang9, Deruo Liu10, Caicun Zhou6, Kwok-Kin Wong11, Lei Yu12, Li Zhang4 and Liang Chen1,2,3,13
1 Graduate School of Peking Union Medical College, Beijing, China
2 National Institute of Biological Sciences, 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
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.