| Literature DB >> 17613438 |
Danan Li1, Takeshi Shimamura, Hongbin Ji, Liang Chen, Henry J Haringsma, Kate McNamara, Mei-Chih Liang, Samanthi A Perera, Sara Zaghlul, Christa L Borgman, Shigeto Kubo, Masaya Takahashi, Yanping Sun, Lucian R Chirieac, Robert F Padera, Neal I Lindeman, Pasi A Jänne, Roman K Thomas, Matthew L Meyerson, Michael J Eck, Jeffrey A Engelman, Geoffrey I Shapiro, Kwok-Kin Wong.
Abstract
The EGFR 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.Entities:
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Year: 2007 PMID： 17613438 DOI： 10.1016/j.ccr.2007.06.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743