Author/Authors :
Li، نويسنده , , Danan and Shimamura، نويسنده , , Takeshi and Ji، نويسنده , , Hongbin and Chen، نويسنده , , Liang and Haringsma، نويسنده , , Henry J. and McNamara، نويسنده , , Kate and Liang، نويسنده , , Mei-Chih and Perera، نويسنده , , Samanthi A. and Zaghlul، نويسنده , , Sara and Borgman، نويسنده , , Christa L. and Kubo، نويسنده , , Shigeto and Takahashi، نويسنده , , Masaya and Sun، نويسنده , , Yanping and Chirieac، نويسنده , , Lucian R. and Padera، نويسنده , , Robert F. and Lindeman، نويسنده , , Neal I. and Jنnne، نويسنده , , Pasi A. and Thomas، نويسنده , , Roman K. and Meyerson، نويسنده , , Matthew L. and Eck، نويسنده , , Michael J. and Engelman، نويسنده , , Jeffrey A. and Shapiro، نويسنده , , Geoffrey I. and Wong، نويسنده , , Kwok-Kin، نويسنده ,
Abstract :
Summary
FR T790M mutation has been identified in tumors from lung cancer patients that eventually develop resistance to erlotinib. In this study, we generated a mouse model with doxycycline-inducible expression of a mutant EGFR containing both L858R, an erlotinib-sensitizing mutation, and the T790M resistance mutation (EGFR TL). Expression of EGFR TL led to development of peripheral adenocarcinomas with bronchioloalveolar features in alveoli as well as papillary adenocarcinomas in bronchioles. Treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI), HKI-272, shrunk only peripheral tumors but not bronchial tumors. However, the combination of HKI-272 and rapamycin resulted in significant regression of both types of lung tumors. This combination therapy may potentially benefit lung cancer patients with the EGFR T790M mutation.
