PMID- 20683448
OWN - NLM
STAT- MEDLINE
DCOM- 20100910
LR  - 20220317
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 103
IP  - 5
DP  - 2010 Aug 24
TI  - Dual inhibition of EGFR and mTOR pathways in small cell lung cancer.
PG  - 622-8
LID - 10.1038/sj.bjc.6605761 [doi]
AB  - BACKGROUND: In this report we investigated the combination of epidermal growth 
      factor receptor (EGFR) and mammalian target of rapamycin (mTOR) pathway 
      inhibition as a possible new therapeutic strategy for small cell lung cancer 
      (SCLC). METHODS: EGFR, p-AKT, p-ERK, p-mTOR and p-p70s6K protein expressions were 
      studied by immunohistochemistry in 107 small cell lung carcinomas and correlated 
      with clinicopathological parameters. Cells of SCLC were treated with 
      erlotinib+/-RAD001 and analysed for cell viability, proliferation, autophagy, and 
      pathway regulation. RESULTS: Epidermal growth factor receptor, p-AKT, p-ERK, 
      p-mTOR, and p-p70s6K were expressed in 37, 24, 13, 55 and 91% of the tumour 
      specimens of all SCLC patients, respectively, and were not associated with 
      disease-free or overall survival. The expression of EGFR was lower in 
      neoadjuvant-treated patients (P=0.038); mTOR pathway activation was higher in the 
      early stages of disease (P=0.048). Coexpression of EGFR/p-mTOR/p-p70s6K was 
      observed in 28% of all patients . EGFR immunoreactivity was associated with p-ERK 
      and p-mTOR expression (P=0.02 and P=0.0001); p-mTOR immunoreactivity was 
      associated with p-p70s6K expression (P=0.001). Tumour cells comprised a 
      functional EGFR, no activating mutations in exons 18-21, and resistance to RAD001 
      monotherapy. We found synergistic effects of erlotinib and RAD001 combination 
      therapy on the molecular level, cell viability, proliferation and autophagy. 
      CONCLUSIONS: The combined inhibition of EGFR/mTOR pathways could be a promising 
      approach to treat SCLC.
FAU - Schmid, K
AU  - Schmid K
AD  - Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
FAU - Bago-Horvath, Z
AU  - Bago-Horvath Z
FAU - Berger, W
AU  - Berger W
FAU - Haitel, A
AU  - Haitel A
FAU - Cejka, D
AU  - Cejka D
FAU - Werzowa, J
AU  - Werzowa J
FAU - Filipits, M
AU  - Filipits M
FAU - Herberger, B
AU  - Herberger B
FAU - Hayden, H
AU  - Hayden H
FAU - Sieghart, W
AU  - Sieghart W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100803
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Quinazolines)
RN  - 0 (Xenopus Proteins)
RN  - 0 (trhd protein, Xenopus)
RN  - 9HW64Q8G6G (Everolimus)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Cell Survival
MH  - Cells, Cultured
MH  - ErbB Receptors/*antagonists & inhibitors
MH  - Erlotinib Hydrochloride
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors
MH  - Lung Neoplasms/drug therapy
MH  - Male
MH  - Middle Aged
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Quinazolines/*administration & dosage
MH  - Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage/*analogs & derivatives
MH  - Small Cell Lung Carcinoma/*drug therapy/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Xenopus Proteins
PMC - PMC2938245
EDAT- 2010/08/05 06:00
MHDA- 2010/09/11 06:00
PMCR- 2011/08/24
CRDT- 2010/08/05 06:00
PHST- 2010/08/05 06:00 [entrez]
PHST- 2010/08/05 06:00 [pubmed]
PHST- 2010/09/11 06:00 [medline]
PHST- 2011/08/24 00:00 [pmc-release]
AID - 6605761 [pii]
AID - 10.1038/sj.bjc.6605761 [doi]
PST - ppublish
SO  - Br J Cancer. 2010 Aug 24;103(5):622-8. doi: 10.1038/sj.bjc.6605761. Epub 2010 Aug 
      3.