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Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells

Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment wit...

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Autores principales: Gruijs, Mandy, Braster, Rens, Overdijk, Marije B., Hellingman, Tessa, Verploegen, Sandra, Korthouwer, Rianne, van der Wilk, Berend J., Parren, Paul W. H. I., van der Vliet, Hans J., Bögels, Marijn, van Egmond, Marjolein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759909/
https://www.ncbi.nlm.nih.gov/pubmed/35035479
http://dx.doi.org/10.1155/2022/3577928
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author Gruijs, Mandy
Braster, Rens
Overdijk, Marije B.
Hellingman, Tessa
Verploegen, Sandra
Korthouwer, Rianne
van der Wilk, Berend J.
Parren, Paul W. H. I.
van der Vliet, Hans J.
Bögels, Marijn
van Egmond, Marjolein
author_facet Gruijs, Mandy
Braster, Rens
Overdijk, Marije B.
Hellingman, Tessa
Verploegen, Sandra
Korthouwer, Rianne
van der Wilk, Berend J.
Parren, Paul W. H. I.
van der Vliet, Hans J.
Bögels, Marijn
van Egmond, Marjolein
author_sort Gruijs, Mandy
collection PubMed
description Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment with specific tumor-targeting monoclonal antibodies (mAb) prevented surgery-induced liver metastasis development in rats. This study investigated whether the epidermal growth factor receptor (EGFR) represents a suitable target for preoperative antibody treatment of colorectal cancer patients undergoing surgery. The majority of patients with resectable colorectal liver metastases were shown to have EGFR + CTCs. Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. Additionally, all three mAbs induced antibody-dependent cellular phagocytosis (ADCP) of tumor cells by macrophages at low antibody concentrations in vitro, independent of mutations in EGFR signaling pathways. The plasma of cetuximab-treated patients efficiently opsonized tumor cells ex vivo and induced phagocytosis. Furthermore, neither proliferation nor migration of epithelial cells was affected in vitro, supporting that wound healing will not be hampered by treatment with low anti-EGFR mAb concentrations. These data support the use of a low dose of anti-EGFR mAbs prior to resection of the tumor to eliminate CTCs without interfering with the healing of the anastomosis. Ultimately, this may reduce the risk of metastasis development, consequently improving long-term patient outcome significantly.
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spelling pubmed-87599092022-01-15 Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells Gruijs, Mandy Braster, Rens Overdijk, Marije B. Hellingman, Tessa Verploegen, Sandra Korthouwer, Rianne van der Wilk, Berend J. Parren, Paul W. H. I. van der Vliet, Hans J. Bögels, Marijn van Egmond, Marjolein J Oncol Research Article Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment with specific tumor-targeting monoclonal antibodies (mAb) prevented surgery-induced liver metastasis development in rats. This study investigated whether the epidermal growth factor receptor (EGFR) represents a suitable target for preoperative antibody treatment of colorectal cancer patients undergoing surgery. The majority of patients with resectable colorectal liver metastases were shown to have EGFR + CTCs. Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. Additionally, all three mAbs induced antibody-dependent cellular phagocytosis (ADCP) of tumor cells by macrophages at low antibody concentrations in vitro, independent of mutations in EGFR signaling pathways. The plasma of cetuximab-treated patients efficiently opsonized tumor cells ex vivo and induced phagocytosis. Furthermore, neither proliferation nor migration of epithelial cells was affected in vitro, supporting that wound healing will not be hampered by treatment with low anti-EGFR mAb concentrations. These data support the use of a low dose of anti-EGFR mAbs prior to resection of the tumor to eliminate CTCs without interfering with the healing of the anastomosis. Ultimately, this may reduce the risk of metastasis development, consequently improving long-term patient outcome significantly. Hindawi 2022-01-07 /pmc/articles/PMC8759909/ /pubmed/35035479 http://dx.doi.org/10.1155/2022/3577928 Text en Copyright © 2022 Mandy Gruijs et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gruijs, Mandy
Braster, Rens
Overdijk, Marije B.
Hellingman, Tessa
Verploegen, Sandra
Korthouwer, Rianne
van der Wilk, Berend J.
Parren, Paul W. H. I.
van der Vliet, Hans J.
Bögels, Marijn
van Egmond, Marjolein
Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells
title Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells
title_full Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells
title_fullStr Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells
title_full_unstemmed Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells
title_short Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells
title_sort epidermal growth factor receptor as target for perioperative elimination of circulating colorectal cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759909/
https://www.ncbi.nlm.nih.gov/pubmed/35035479
http://dx.doi.org/10.1155/2022/3577928
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