Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:35284.

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

Naiqing Xu, Wenfeng Fang, Libing Mu, Yanna Tang, Lei Gao, Shengxiang Ren, Dengfeng Cao, Lixin Zhou, Aiqun Zhang, Deruo Liu, Caicun Zhou, Kwok-Kin Wong, Lei Yu, Li Zhang and Liang Chen _

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Oncotarget. 2016; 7:3884-3896. https://doi.org/10.18632/oncotarget.6461

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Abstract

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

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.


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