@article{dc5dc18061b140cb9ef7491655ca1684,
title = "Bronchial and Peripheral Murine Lung Carcinomas Induced by T790M-L858R Mutant EGFR Respond to HKI-272 and Rapamycin Combination Therapy",
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.",
keywords = "CELLCYCLE, CHEMBIO, SIGNALING",
author = "Danan Li and Takeshi Shimamura and Hongbin Ji and Liang Chen and Haringsma, {Henry J.} and Kate McNamara and Liang, {Mei Chih} and Perera, {Samanthi A.} and Sara Zaghlul and Borgman, {Christa L.} and Shigeto Kubo and Masaya Takahashi and Yanping Sun and Chirieac, {Lucian R.} and Padera, {Robert F.} and Lindeman, {Neal I.} and J{\"a}nne, {Pasi A.} and Thomas, {Roman K.} and Meyerson, {Matthew L.} and Eck, {Michael J.} and Engelman, {Jeffrey A.} and Shapiro, {Geoffrey I.} and Wong, {Kwok Kin}",
note = "Funding Information: We thank Dr. William Pao and Dr. Maureen Zakowski for confirmation of histological analyses in our animal model; Dr. Jeffrey Whitsett for providing the CCSP-rtTA transgenic mice. We also thank Christine Lam and Mei Zheng for technical supports. This work was supported by the Sidney Kimmel Foundation for Cancer Research (K.-K.W.); the Joan Scarangello Foundation to Conquer Lung Cancer (K.-K.W.); the Flight Attendant Medical Research Institute (K.-K.W.); and NIH grants K08 AG024004 (K.-K.W.), R01 AG2400401 (K.-K.W.), R01 CA122794 (K.-K.W.), P20 CA90578 (G.I.S. and L.R.C.), and R01 CA90687 (G.I.S.). T.S. is supported by a Career Development Award as part of the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence (SPORE) in Lung Cancer, and NIH grant P20 CA90578. ",
year = "2007",
month = jul,
day = "10",
doi = "10.1016/j.ccr.2007.06.005",
language = "English (US)",
volume = "12",
pages = "81--93",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}