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Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230

Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of...

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Autores principales: Blackwell, Christina, Sherk, Christian, Fricko, Maggie, Ganji, Gopinath, Barnette, Mary, Hoang, Bao, Tunstead, James, Skedzielewski, Tina, Alsaid, Hasan, Jucker, Beat M., Minthorn, Elisabeth, Kumar, Rakesh, DeYoung, M. Phillip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129976/
https://www.ncbi.nlm.nih.gov/pubmed/27223434
http://dx.doi.org/10.18632/oncotarget.9515
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author Blackwell, Christina
Sherk, Christian
Fricko, Maggie
Ganji, Gopinath
Barnette, Mary
Hoang, Bao
Tunstead, James
Skedzielewski, Tina
Alsaid, Hasan
Jucker, Beat M.
Minthorn, Elisabeth
Kumar, Rakesh
DeYoung, M. Phillip
author_facet Blackwell, Christina
Sherk, Christian
Fricko, Maggie
Ganji, Gopinath
Barnette, Mary
Hoang, Bao
Tunstead, James
Skedzielewski, Tina
Alsaid, Hasan
Jucker, Beat M.
Minthorn, Elisabeth
Kumar, Rakesh
DeYoung, M. Phillip
author_sort Blackwell, Christina
collection PubMed
description Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of mesothelioma, a tumor type shown to express high levels of FGF2 and FGFR1. GSK3052230 demonstrated antiproliferative activity across a panel of mesothelioma cell lines and inhibited growth of tumor xenografts in mice. High expression of FGF2 and FGFR1 correlated well with response to FGF pathway inhibition. GSK3052230 inhibited MAPK signaling as evidenced by decreased phospho-ERK and phospho-S6 levels in vitro and in vivo. Additionally, dose-dependent and statistically-significant reductions in tumor vessel density were observed in GSK3052230-treated tumors compared to vehicle-treated tumors. These data support the role of GSK3052230 in effectively targeting FGF-FGFR autocrine signaling in mesothelioma, demonstrate its impact on tumor growth and angiogenesis, and provide a rationale for the current clinical evaluation of this molecule in mesothelioma patients.
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spelling pubmed-51299762016-12-11 Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 Blackwell, Christina Sherk, Christian Fricko, Maggie Ganji, Gopinath Barnette, Mary Hoang, Bao Tunstead, James Skedzielewski, Tina Alsaid, Hasan Jucker, Beat M. Minthorn, Elisabeth Kumar, Rakesh DeYoung, M. Phillip Oncotarget Research Paper Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of mesothelioma, a tumor type shown to express high levels of FGF2 and FGFR1. GSK3052230 demonstrated antiproliferative activity across a panel of mesothelioma cell lines and inhibited growth of tumor xenografts in mice. High expression of FGF2 and FGFR1 correlated well with response to FGF pathway inhibition. GSK3052230 inhibited MAPK signaling as evidenced by decreased phospho-ERK and phospho-S6 levels in vitro and in vivo. Additionally, dose-dependent and statistically-significant reductions in tumor vessel density were observed in GSK3052230-treated tumors compared to vehicle-treated tumors. These data support the role of GSK3052230 in effectively targeting FGF-FGFR autocrine signaling in mesothelioma, demonstrate its impact on tumor growth and angiogenesis, and provide a rationale for the current clinical evaluation of this molecule in mesothelioma patients. Impact Journals LLC 2016-05-20 /pmc/articles/PMC5129976/ /pubmed/27223434 http://dx.doi.org/10.18632/oncotarget.9515 Text en Copyright: © 2016 Blackwell et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Blackwell, Christina
Sherk, Christian
Fricko, Maggie
Ganji, Gopinath
Barnette, Mary
Hoang, Bao
Tunstead, James
Skedzielewski, Tina
Alsaid, Hasan
Jucker, Beat M.
Minthorn, Elisabeth
Kumar, Rakesh
DeYoung, M. Phillip
Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230
title Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230
title_full Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230
title_fullStr Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230
title_full_unstemmed Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230
title_short Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230
title_sort inhibition of fgf/fgfr autocrine signaling in mesothelioma with the fgf ligand trap, fp-1039/gsk3052230
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129976/
https://www.ncbi.nlm.nih.gov/pubmed/27223434
http://dx.doi.org/10.18632/oncotarget.9515
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