| Author |
Liu, Zhentao Shen, Zhirong Bai, Hua Zhang, Zemin Zhao, Jun Wang, Xiaodong Duan, Jianchun Wang, Zhijie Fu, Shuai Li, Zhenxiang Wang, Jie |
| Description |
Author Affiliation: Wang Z ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); Shen Z ( National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing 102206, China); Li Z ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); Duan J ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); Fu S ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); Liu Z ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); Bai H ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); Zhang Z ( Biodynamic Optical Imaging Center, Integrated Science Research Center, Peking University, Beijing 100871, China.); Zhao J ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); Wang X ( National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing 102206, China); Wang J ( Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Beijing Institute for Cancer Research, Beijing 100142, China); |
| 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-AKT-mTOR 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. |
| Subject Keyword |
Bone Morphogenetic Protein Receptors Metabolism Bone Morphogenetic Proteins Carcinoma, Squamous Cell Genetics Drug Resistance, Neoplasm Lung Neoplasms Mutation Protein Kinase Inhibitors Therapeutic Use Receptor, Epidermal Growth Factor Adenocarcinoma Drug Therapy Animals Carcinoma, Non-Small-Cell Lung Immunohistochemistry Mice, Nude Multivariate Analysis Reproducibility Of Results Ribosomal Protein S6 Kinases, 70-kDa Signal Transduction Smad Proteins Research Support, Non-U.S. Gov't Multidisciplinary |
