Oncotarget

Research Papers:

EGFR G796D mutation mediates resistance to osimertinib

Di Zheng, Min Hu, Yu Bai, Xuehua Zhu, Xuesong Lu, Chunyan Wu, Jiying Wang, Li Liu, Zheng Wang, Jian Ni, Zhenfan Yang and Jianfang Xu _

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Oncotarget. 2017; 8:49671-49679. https://doi.org/10.18632/oncotarget.17913

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Abstract

Di Zheng1,*, Min Hu2,*, Yu Bai2, Xuehua Zhu2, Xuesong Lu3, Chunyan Wu4, Jiying Wang1, Li Liu1, Zheng Wang3, Jian Ni1, Zhenfan Yang2 and Jianfang Xu1

1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China

2IMED Asia, AstraZeneca, Shanghai, China

3Research and Development Information, AstraZeneca, Shanghai, China

4Department of Pathology, Shanghai Pulmonary Hospital, Tongji University Medical School, Shanghai, China

*These authors contributed equally to this work

Correspondence to:

Jianfang Xu, email: xujianfang63@aliyun.com

Zhenfan Yang, email: Pamela.Yang@astrazeneca.com

Keywords: EGFR, NSCLC, osimertinib, drug resistance, G796D

Received: March 08, 2017     Accepted: May 04, 2017     Published: May 16, 2017

ABSTRACT

Osimertinib is an effective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in multiple countries and regions for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Despite impressive initial tumor responses, development of drug resistance ultimately limits the benefit of this compound. Mechanisms of resistance to osimertinib are just beginning to emerge, such as EGFR C797S and L718Q mutations, BRAF V600E and PIK3CA E545K mutations, as well as ERBB2 and MET amplification. However, a comprehensive view is still missing. In this study, we presented the first case of Chinese NSCLC patient who developed resistance to osimertinib, and discovered de novo EGFR G796D mutation as a potential mechanism. Our findings provided insights into mechanisms of resistance to osimertinib and highlighted tumor heterogeneity and clonal evolution during the development of drug resistance.


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