PMID- 27267852
OWN - NLM
STAT- MEDLINE
DCOM- 20180112
LR  - 20191008
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 22
IP  - 24
DP  - 2016 Dec 15
TI  - Targeting Estrogen Receptor Signaling with Fulvestrant Enhances Immune and 
      Chemotherapy-Mediated Cytotoxicity of Human Lung Cancer.
PG  - 6204-6216
AB  - PURPOSE: The conversion of tumor cells from an epithelial to a mesenchymal-like 
      phenotype, via a process designated as the epithelial-mesenchymal transition 
      (EMT), is known to mediate tumor resistance to a variety of cell death inducers, 
      including cytotoxic effector immune cells. The goal of this study was to identify 
      and potentially repurpose FDA-approved compounds capable of reducing mesenchymal 
      features of human lung carcinoma cells, which could be used in combination with 
      immunotherapies or chemotherapeutic strategies to improve clinical responses. 
      EXPERIMENTAL DESIGN: In the current report, we have utilized a quantitative 
      high-throughput screening (qHTS) of a pharmaceutical collection of more than 
      2,000 compounds to identify clinically approved drugs capable of augmenting the 
      sensitivity of mesenchymal-like, lung cancer cells to immune- and 
      chemotherapy-mediated lysis, both in vitro and in vivo RESULTS: The estrogen 
      receptor antagonist fulvestrant was shown to reduce mesenchymal features of lung 
      carcinoma cells, resulting in tumor sensitization to the cytotoxic effect of 
      antigen-specific T cells, natural killer (NK) effector cells, and chemotherapy 
      both in vivo and in vitro CONCLUSIONS: To our knowledge, this is the first report 
      defining a potential role for estrogenic signaling in promoting tumor resistance 
      to immune-mediated cytotoxicity and chemotherapy in lung cancer. Our data 
      demonstrate a robust association between the acquisition of mesenchymal 
      attributes, therapeutic resistance of lung carcinoma cells, and the expression of 
      estrogen receptor 1 (ESR1), supporting further investigations on the role of 
      estrogen signaling in lung cancer progression via the induction of EMT. Clin 
      Cancer Res; 22(24); 6204-16. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Hamilton, Duane H
AU  - Hamilton DH
AD  - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National 
      Cancer Institute, NIH, Bethesda, Maryland.
FAU - Griner, Lesley Mathews
AU  - Griner LM
AD  - National Center for Advancing Translational Sciences, NIH, Rockville, Maryland.
FAU - Keller, Jonathan M
AU  - Keller JM
AD  - National Center for Advancing Translational Sciences, NIH, Rockville, Maryland.
FAU - Hu, Xin
AU  - Hu X
AD  - National Center for Advancing Translational Sciences, NIH, Rockville, Maryland.
FAU - Southall, Noel
AU  - Southall N
AD  - National Center for Advancing Translational Sciences, NIH, Rockville, Maryland.
FAU - Marugan, Juan
AU  - Marugan J
AD  - National Center for Advancing Translational Sciences, NIH, Rockville, Maryland.
FAU - David, Justin M
AU  - David JM
AD  - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National 
      Cancer Institute, NIH, Bethesda, Maryland.
FAU - Ferrer, Marc
AU  - Ferrer M
AD  - National Center for Advancing Translational Sciences, NIH, Rockville, Maryland.
FAU - Palena, Claudia
AU  - Palena C
AD  - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National 
      Cancer Institute, NIH, Bethesda, Maryland. palenac@mail.nih.gov.
LA  - eng
GR  - ZIC BC010937-03/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20160607
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Estrogen Receptor alpha)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm/drug effects/immunology
MH  - Epithelial-Mesenchymal Transition/drug effects/immunology
MH  - Estradiol/*analogs & derivatives/pharmacology
MH  - Estrogen Receptor alpha/*metabolism
MH  - Fulvestrant
MH  - Humans
MH  - Killer Cells, Natural/drug effects/immunology
MH  - Lung Neoplasms/*drug therapy/*immunology/metabolism
MH  - Signal Transduction/*drug effects/immunology
MH  - T-Lymphocytes/drug effects/immunology
PMC - PMC5143224
MID - NIHMS794586
COIS- The authors have no conflict of interest to declare.
EDAT- 2016/06/09 06:00
MHDA- 2018/01/13 06:00
PMCR- 2017/12/15
CRDT- 2016/06/09 06:00
PHST- 2015/12/21 00:00 [received]
PHST- 2016/05/09 00:00 [revised]
PHST- 2016/05/24 00:00 [accepted]
PHST- 2016/06/09 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
PHST- 2016/06/09 06:00 [entrez]
PHST- 2017/12/15 00:00 [pmc-release]
AID - 1078-0432.CCR-15-3059 [pii]
AID - 10.1158/1078-0432.CCR-15-3059 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2016 Dec 15;22(24):6204-6216. doi: 
      10.1158/1078-0432.CCR-15-3059. Epub 2016 Jun 7.