@article{b6c363dbdc814d3fa67077364c9e8217,
title = "Rapamycin Prevents the Development and Progression of Mutant Epidermal Growth Factor Receptor Lung Tumors with the Acquired Resistance Mutation T790M",
abstract = "Lung cancer in never-smokers is an important disease often characterized by mutations in epidermal growth factor receptor (EGFR), yet risk reduction measures and effective chemopreventive strategies have not been established. We identify mammalian target of rapamycin (mTOR) as potentially valuable target for EGFR mutant lung cancer. mTOR is activated in human lung cancers with EGFR mutations, and this increases with acquisition of T790M mutation. In a mouse model of EGFR mutant lung cancer, mTOR activation is an early event. As a single agent, the mTOR inhibitor rapamycin prevents tumor development, prolongs overall survival, and improves outcomes after treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI). These studies support clinical testing of mTOR inhibitors in order to prevent the development and progression of EGFR mutant lung cancers.",
author = "Shigeru Kawabata and Mercado-Matos, {Jos{\'e} R.} and Hollander, {M. Christine} and Danielle Donahue and Willie Wilson and Lucia Regales and Mohit Butaney and William Pao and Wong, {Kwok Kin} and J{\"a}nne, {Pasi A.} and Dennis, {Phillip A.}",
note = "Funding Information: The authors would like to thank Maiga Emmanuel (Office of the Director, NCI) for assistance with genotyping; Morales-Contreras Juan, Dumas Tarra, and Dr. John U. Dennis (Laboratory Animal Medicine, NCI) for veterinary services; Dr. Jeffrey A. Whitsett (University of Cincinnati College of Medicine) for providing CCSP-rtTA transgenic mice; Dr. Nathanael S. Gray (Harvard Medical School) for providing WZ4002 compound; and the NIH Fellows Editorial Board for editorial assistance. This research was supported by the Intramural Research Program of the NIH, NCI, and CCR (P.A.D.) and NIH R01CA135257 (P.A.J.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Publication of this article was funded in part by the Open Access Promotion Fund of the Johns Hopkins University Libraries. ",
year = "2014",
month = jun,
day = "26",
doi = "10.1016/j.celrep.2014.05.039",
language = "English (US)",
volume = "7",
pages = "1824--1832",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}