The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1

Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cel...

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Main Authors:	Wang, Xiaoen, Bullock, Andrea J., Zhang, Liang, Wei, Lin, Yu, Dongyin, Mahagaokar, Kedar, Alsop, David C., Mier, James W., Atkins, Michael B., Coxon, Angela, Oliner, Jon, Bhatt, Rupal S.
Format:	Online
Language:	English
Published:	Neoplasia Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101387/

id	pubmed-4101387
recordtype	oai_dc
spelling	pubmed-41013872014-07-24 The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1 Wang, Xiaoen Bullock, Andrea J. Zhang, Liang Wei, Lin Yu, Dongyin Mahagaokar, Kedar Alsop, David C. Mier, James W. Atkins, Michael B. Coxon, Angela Oliner, Jon Bhatt, Rupal S. Article Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cell carcinoma (mRCC). We measured Ang2 expression in human tissue and plasma, and tested the effect of dual Ang1/2 (trebananib; AMG386) or Ang2 alone (L1-7) inhibition with VEGFR inhibition on murine RCC growth and blood flow. Ang2 levels were higher in human tumors than normal tissues with RCC ranking highest for Ang2 expression across all tumor types tested. Plasma Ang2 was significantly higher in patients with mRCC compared to controls or patients with stage I disease. Plasma Ang2 decreased with sunitinib treatment and increased at time of disease progression. In the RCC mouse, dual Ang1/2 and Ang2 inhibition improved the activity of sunitinib. Combined Ang1/2 and VEGFR inhibition prevented the resumption of blood flow associated with sunitinib resistance. Thus, Ang2 inhibition, independent of Ang1 inhibition, improves the activity of sunitinib and plasma Ang2 increases in the setting of progression on sunitinib possibly contributing to resistance. Further, arterial spin-labeled perfusion magnetic resonance imaging might be a non-invasive marker of the antiangiogenic activity of Ang inhibitors. Neoplasia Press 2014-03-04 /pmc/articles/PMC4101387/ /pubmed/24704536 http://dx.doi.org/10.1016/j.tranon.2014.02.003 Text en Copyright © 2014 Neoplasia Press, Inc. All rights reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Xiaoen Bullock, Andrea J. Zhang, Liang Wei, Lin Yu, Dongyin Mahagaokar, Kedar Alsop, David C. Mier, James W. Atkins, Michael B. Coxon, Angela Oliner, Jon Bhatt, Rupal S.
spellingShingle	Wang, Xiaoen Bullock, Andrea J. Zhang, Liang Wei, Lin Yu, Dongyin Mahagaokar, Kedar Alsop, David C. Mier, James W. Atkins, Michael B. Coxon, Angela Oliner, Jon Bhatt, Rupal S. The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1
author_facet	Wang, Xiaoen Bullock, Andrea J. Zhang, Liang Wei, Lin Yu, Dongyin Mahagaokar, Kedar Alsop, David C. Mier, James W. Atkins, Michael B. Coxon, Angela Oliner, Jon Bhatt, Rupal S.
author_sort	Wang, Xiaoen
title	The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1
title_short	The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1
title_full	The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1
title_fullStr	The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1
title_full_unstemmed	The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1
title_sort	role of angiopoietins as potential therapeutic targets in renal cell carcinoma1
description	Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cell carcinoma (mRCC). We measured Ang2 expression in human tissue and plasma, and tested the effect of dual Ang1/2 (trebananib; AMG386) or Ang2 alone (L1-7) inhibition with VEGFR inhibition on murine RCC growth and blood flow. Ang2 levels were higher in human tumors than normal tissues with RCC ranking highest for Ang2 expression across all tumor types tested. Plasma Ang2 was significantly higher in patients with mRCC compared to controls or patients with stage I disease. Plasma Ang2 decreased with sunitinib treatment and increased at time of disease progression. In the RCC mouse, dual Ang1/2 and Ang2 inhibition improved the activity of sunitinib. Combined Ang1/2 and VEGFR inhibition prevented the resumption of blood flow associated with sunitinib resistance. Thus, Ang2 inhibition, independent of Ang1 inhibition, improves the activity of sunitinib and plasma Ang2 increases in the setting of progression on sunitinib possibly contributing to resistance. Further, arterial spin-labeled perfusion magnetic resonance imaging might be a non-invasive marker of the antiangiogenic activity of Ang inhibitors.
publisher	Neoplasia Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101387/
_version_	1613114949287018496

The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma1

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