| Title | Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations |
| Authors | Wang, Zhijie Shen, Zhirong Li, Zhenxiang Duan, Jianchun Fu, Shuai Liu, Zhentao Bai, Hua Zhang, Zemin Zhao, Jun Wang, Xiaodong Wang, Jie |
| Affiliation | Beijing Canc Hosp, Minist Educ, Key Lab Carcinogenesis & Translat Res, Dept Thorac Med Oncol, Beijing 100142, Peoples R China. Beijing Inst Canc Res, Beijing 100142, Peoples R China. Natl Inst Biol Sci, Beijing 102206, Peoples R China. Shanghai Jiao Tong Univ, Sch Med, Collaborat Innovat Ctr Syst Biomed, Shanghai 200240, Peoples R China. Shandong Acad Med Sci, Dept Radiat Oncol, Shandong Canc Hosp & Inst, Jinan 250117, Peoples R China. Peking Univ, Biodynam Opt Imaging Ctr, Integrated Sci Res Ctr, Beijing 100871, Peoples R China. |
| Keywords | epidermal growth factor receptor tyrosine kinase inhibitor lung squamous cell carcinoma bone morphogenetic proteins drug resistance FACTOR RECEPTOR MUTATIONS 1ST-LINE TREATMENT CANCER PATIENTS OPEN-LABEL ERLOTINIB GEFITINIB ADENOCARCINOMA CHEMOTHERAPY KINASE CLASSIFICATION |
| Issue Date | 2015 |
| Publisher | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
| Citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2015,112,(32),9990-9995. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/417232 |
| ISSN | 0027-8424 |
| DOI | 10.1073/pnas.1510837112 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生物医学前沿创新中心 |
