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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4947705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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