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Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab

BACKGROUND: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use. METHODS: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of ca...

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Autores principales: Zhou, Cong, Clamp, Andrew, Backen, Alison, Berzuini, Carlo, Renehan, Andrew, Banks, Rosamonde E, Kaplan, Richard, Scherer, Stefan J, Kristensen, Gunnar B, Pujade-Lauraine, Eric, Dive, Caroline, Jayson, Gordon C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947705/
https://www.ncbi.nlm.nih.gov/pubmed/27351218
http://dx.doi.org/10.1038/bjc.2016.194
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author Zhou, Cong
Clamp, Andrew
Backen, Alison
Berzuini, Carlo
Renehan, Andrew
Banks, Rosamonde E
Kaplan, Richard
Scherer, Stefan J
Kristensen, Gunnar B
Pujade-Lauraine, Eric
Dive, Caroline
Jayson, Gordon C
author_facet Zhou, Cong
Clamp, Andrew
Backen, Alison
Berzuini, Carlo
Renehan, Andrew
Banks, Rosamonde E
Kaplan, Richard
Scherer, Stefan J
Kristensen, Gunnar B
Pujade-Lauraine, Eric
Dive, Caroline
Jayson, Gordon C
author_sort Zhou, Cong
collection PubMed
description BACKGROUND: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use. METHODS: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of carboplatin and paclitaxel with or without bevacizumab. Plasma concentrations of 15 circulating angio-biomarkers were measured using a validated multiplex ELISA, analysed through a novel network analysis and their relevance to the PFS then determined. RESULTS: Samples (n=650) were analysed from 92 patients. Bevacizumab induced correlative relationships between Ang1 and Tie2 plasma concentrations, which reduced after initiation of treatment and remained decreased until progressive disease occurred. A 50% increase from the nadir in the concentration of circulating Tie2 (or the product of circulating Ang1 and Tie2) predicted tumour progression. Combining Tie2 with GCIG-defined Ca125 data yielded a significant improvement in the prediction of progressive disease in patients receiving bevacizumab in comparison with Ca125 alone (74.1% vs 47.3%, P<1 × 10(−9)). CONCLUSIONS: Tie2 is a vascular progression marker for bevacizumab-treated ovarian cancer patients. Tie2 in combination with Ca125 provides superior information to clinicians on progressive disease in patients with VEGFi-treated ovarian cancers.
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spelling pubmed-49477052016-07-27 Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab Zhou, Cong Clamp, Andrew Backen, Alison Berzuini, Carlo Renehan, Andrew Banks, Rosamonde E Kaplan, Richard Scherer, Stefan J Kristensen, Gunnar B Pujade-Lauraine, Eric Dive, Caroline Jayson, Gordon C Br J Cancer Molecular Diagnostics BACKGROUND: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use. METHODS: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of carboplatin and paclitaxel with or without bevacizumab. Plasma concentrations of 15 circulating angio-biomarkers were measured using a validated multiplex ELISA, analysed through a novel network analysis and their relevance to the PFS then determined. RESULTS: Samples (n=650) were analysed from 92 patients. Bevacizumab induced correlative relationships between Ang1 and Tie2 plasma concentrations, which reduced after initiation of treatment and remained decreased until progressive disease occurred. A 50% increase from the nadir in the concentration of circulating Tie2 (or the product of circulating Ang1 and Tie2) predicted tumour progression. Combining Tie2 with GCIG-defined Ca125 data yielded a significant improvement in the prediction of progressive disease in patients receiving bevacizumab in comparison with Ca125 alone (74.1% vs 47.3%, P<1 × 10(−9)). CONCLUSIONS: Tie2 is a vascular progression marker for bevacizumab-treated ovarian cancer patients. Tie2 in combination with Ca125 provides superior information to clinicians on progressive disease in patients with VEGFi-treated ovarian cancers. Nature Publishing Group 2016-07-12 2016-06-28 /pmc/articles/PMC4947705/ /pubmed/27351218 http://dx.doi.org/10.1038/bjc.2016.194 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Molecular Diagnostics
Zhou, Cong
Clamp, Andrew
Backen, Alison
Berzuini, Carlo
Renehan, Andrew
Banks, Rosamonde E
Kaplan, Richard
Scherer, Stefan J
Kristensen, Gunnar B
Pujade-Lauraine, Eric
Dive, Caroline
Jayson, Gordon C
Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab
title Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab
title_full Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab
title_fullStr Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab
title_full_unstemmed Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab
title_short Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab
title_sort systematic analysis of circulating soluble angiogenesis-associated proteins in icon7 identifies tie2 as a biomarker of vascular progression on bevacizumab
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947705/
https://www.ncbi.nlm.nih.gov/pubmed/27351218
http://dx.doi.org/10.1038/bjc.2016.194
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