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

Autor: Mandy Gruijs, Rens Braster, Marije B. Overdijk, Tessa Hellingman, Sandra Verploegen, Rianne Korthouwer, Berend J. van der Wilk, Paul W. H. I. Parren, Hans J. van der Vliet, Marijn Bögels, Marjolein van Egmond
Přispěvatelé: Molecular cell biology and Immunology, Surgery, Internal medicine, CCA - Cancer biology and immunology
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Oncology
Journal of Oncology, 2022. HINDAWI LTD
Journal of oncology, 2022:3577928. Hindawi Publishing Corporation
Gruijs, M, Braster, R, Overdijk, M B, Hellingman, T, Verploegen, S, Korthouwer, R, van der Wilk, B J, Parren, P W H I, van der Vliet, H J, Bögels, M & van Egmond, M 2022, ' Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells ', Journal of oncology, vol. 2022, 3577928, pp. 3577928 . https://doi.org/10.1155/2022/3577928
Journal of Oncology, Vol 2022 (2022)
ISSN: 1687-8469
1687-8450
Popis: 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.
Databáze: OpenAIRE
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