PMID- 24931608
OWN - NLM
STAT- MEDLINE
DCOM- 20150416
LR  - 20211203
IS  - 2211-1247 (Electronic)
VI  - 7
IP  - 6
DP  - 2014 Jun 26
TI  - Rapamycin prevents the development and progression of mutant epidermal growth 
      factor receptor lung tumors with the acquired resistance mutation T790M.
PG  - 1824-32
LID - S2211-1247(14)00433-1 [pii]
LID - 10.1016/j.celrep.2014.05.039 [doi]
AB  - 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.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kawabata, Shigeru
AU  - Kawabata S
AD  - Department of Oncology, Johns Hopkins Bayview Medical Center, Baltimore, MD 
      21224, USA.
FAU - Mercado-Matos, Jose R
AU  - Mercado-Matos JR
AD  - Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD 20892, USA.
FAU - Hollander, M Christine
AU  - Hollander MC
AD  - Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD 20892, USA.
FAU - Donahue, Danielle
AU  - Donahue D
AD  - Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, 
      National Institutes of Health (NIH), Bethesda, MD 20892, USA.
FAU - Wilson, Willie 3rd
AU  - Wilson W 3rd
AD  - Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD 20892, USA.
FAU - Regales, Lucia
AU  - Regales L
AD  - Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
FAU - Butaney, Mohit
AU  - Butaney M
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, 
      USA.
FAU - Pao, William
AU  - Pao W
AD  - Division of Hematology-Oncology, Department of Medicine, Vanderbilt-Ingram Cancer 
      Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
FAU - Wong, Kwok-Kin
AU  - Wong KK
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, 
      USA.
FAU - Janne, Pasi A
AU  - Janne PA
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, 
      USA.
FAU - Dennis, Phillip A
AU  - Dennis PA
AD  - Department of Oncology, Johns Hopkins Bayview Medical Center, Baltimore, MD 
      21224, USA. Electronic address: pdennis@jhmi.edu.
LA  - eng
GR  - P30 CA006973/CA/NCI NIH HHS/United States
GR  - P01 CA154303/CA/NCI NIH HHS/United States
GR  - R01 CA121210/CA/NCI NIH HHS/United States
GR  - R01 CA140594/CA/NCI NIH HHS/United States
GR  - R01 CA135257/CA/NCI NIH HHS/United States
GR  - ZIA SC010292-14/Intramural NIH HHS/United States
GR  - R01 CA166480/CA/NCI NIH HHS/United States
GR  - R01CA135257/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140612
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Antibiotics, Antineoplastic)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Disease Progression
MH  - Drug Resistance, Neoplasm
MH  - ErbB Receptors/*genetics/metabolism
MH  - Humans
MH  - Lung Neoplasms/enzymology/genetics/*prevention & control
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Random Allocation
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4110638
MID - NIHMS601044
EDAT- 2014/06/17 06:00
MHDA- 2015/04/17 06:00
PMCR- 2015/06/26
CRDT- 2014/06/17 06:00
PHST- 2014/01/27 00:00 [received]
PHST- 2014/04/17 00:00 [revised]
PHST- 2014/05/18 00:00 [accepted]
PHST- 2014/06/17 06:00 [entrez]
PHST- 2014/06/17 06:00 [pubmed]
PHST- 2015/04/17 06:00 [medline]
PHST- 2015/06/26 00:00 [pmc-release]
AID - S2211-1247(14)00433-1 [pii]
AID - 10.1016/j.celrep.2014.05.039 [doi]
PST - ppublish
SO  - Cell Rep. 2014 Jun 26;7(6):1824-32. doi: 10.1016/j.celrep.2014.05.039. Epub 2014 
      Jun 12.