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学科主题临床医学
Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations
Wang, Zhijie1,2; Shen, Zhirong3,4; Li, Zhenxiang1,2,5; Duan, Jianchun1,2; Fu, Shuai1,2; Liu, Zhentao1,2; Bai, Hua1,2; Zhang, Zemin6; Zhao, Jun1,2; Wang, Xiaodong3,4; Wang, Jie1,2
关键词epidermal growth factor receptor tyrosine kinase inhibitor lung squamous cell carcinoma bone morphogenetic proteins drug resistance
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2015-08-11
DOI10.1073/pnas.1510837112
112期:32页:9990-9995
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]FACTOR RECEPTOR MUTATIONS ; 1ST-LINE TREATMENT ; CANCER PATIENTS ; OPEN-LABEL ; ERLOTINIB ; GEFITINIB ; ADENOCARCINOMA ; CHEMOTHERAPY ; KINASE ; CLASSIFICATION
英文摘要

The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non-small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKTmTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations.

语种英语
WOS记录号WOS:000359285100065
项目编号xx2014B051 ; xx2012070 ; 2010CB835400 ; 2012CB837400 ; 81330062 ; IRT13003 ; SS2015AA020403 ; Z141100000214013 ; 2013D003034000019
资助机构Beijing Nova Program from the Beijing Municipal Commission of Science and Technology ; National Basic Science 973 from the Chinese Ministry of Science and Technology ; National Natural Sciences Foundation Key Program ; Education Ministry Innovative Research Team Program ; Fund for Peking University-Tsinghua University Joint Center for Life Sciences Clinical Investigator ; Special Research Foundation of State Key Laboratory of Medical Genomics ; National High Technology Research and Development Program 863 ; Beijing Technology Project ; Center for Molecular and Translational Medicine ; Collaborative Innovation Center for Cancer Medicine ; Special Research Foundation for the Doctoral Program of Higher Education ; Beijing Excellent Talents Project
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66439
专题北京大学临床肿瘤学院_胸部肿瘤内科
作者单位1.Beijing Canc Hosp, Minist Educ, Key Lab Carcinogenesis & Translat Res, Dept Thorac Med Oncol, Beijing 100142, Peoples R China
2.Beijing Inst Canc Res, Beijing 100142, Peoples R China
3.Natl Inst Biol Sci, Beijing 102206, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Med, Collaborat Innovat Ctr Syst Biomed, Shanghai 200240, Peoples R China
5.Shandong Acad Med Sci, Dept Radiat Oncol, Shandong Canc Hosp & Inst, Jinan 250117, Peoples R China
6.Peking Univ, Biodynam Opt Imaging Ctr, Integrated Sci Res Ctr, Beijing 100871, Peoples R China
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GB/T 7714
Wang, Zhijie,Shen, Zhirong,Li, Zhenxiang,et al. Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(32):9990-9995.
APA Wang, Zhijie.,Shen, Zhirong.,Li, Zhenxiang.,Duan, Jianchun.,Fu, Shuai.,...&Wang, Jie.(2015).Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,112(32),9990-9995.
MLA Wang, Zhijie,et al."Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.32(2015):9990-9995.
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