OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer

Abstract c-MET is considered a driver of cancer progression, impacting tumor growth and tumor-supporting stroma. Here, we investigated the therapeutic efficacy of OMO-1, a potent and selective c-MET inhibitor, in an immunocompetent intraductal mouse model for triple-negative breast cancer (TNBC). OM...

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Autores principales:	Jonas Steenbrugge, Niels Vander Elst, Kristel Demeyere, Olivier De Wever, Niek N. Sanders, Wim Van Den Broeck, Eric Ciamporcero, Timothy Perera, Evelyne Meyer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b9aac903f53b496da8763625e4385c99
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spelling	oai:doaj.org-article:b9aac903f53b496da8763625e4385c992021-12-02T17:03:34ZOMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer10.1038/s41523-021-00234-82374-4677https://doaj.org/article/b9aac903f53b496da8763625e4385c992021-03-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00234-8https://doaj.org/toc/2374-4677Abstract c-MET is considered a driver of cancer progression, impacting tumor growth and tumor-supporting stroma. Here, we investigated the therapeutic efficacy of OMO-1, a potent and selective c-MET inhibitor, in an immunocompetent intraductal mouse model for triple-negative breast cancer (TNBC). OMO-1 reduced non-c-MET addicted 4T1 tumor progression dose dependently as monotherapeutic and provided additional disease reduction in combination with cisplatin. At the stromal level, OMO-1 significantly reduced neutrophil infiltration in 4T1 tumors, promoted immune activation, and enhanced cisplatin-mediated reduction of tumor-associated macrophages. OMO-1 treatment also reduced 4T1 tumor hypoxia and increased expression of pericyte markers, indicative for vascular maturation. Corroborating this finding, cisplatin delivery to the 4T1 primary tumor was enhanced upon OMO-1 treatment, increasing cisplatin DNA-adduct levels and tumor cell death. Although verification in additional cell lines is warranted, our findings provide initial evidence that TNBC patients may benefit from OMO-1 treatment, even in cases of non-c-MET addicted tumors.Jonas SteenbruggeNiels Vander ElstKristel DemeyereOlivier De WeverNiek N. SandersWim Van Den BroeckEric CiamporceroTimothy PereraEvelyne MeyerNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jonas Steenbrugge Niels Vander Elst Kristel Demeyere Olivier De Wever Niek N. Sanders Wim Van Den Broeck Eric Ciamporcero Timothy Perera Evelyne Meyer OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer
description	Abstract c-MET is considered a driver of cancer progression, impacting tumor growth and tumor-supporting stroma. Here, we investigated the therapeutic efficacy of OMO-1, a potent and selective c-MET inhibitor, in an immunocompetent intraductal mouse model for triple-negative breast cancer (TNBC). OMO-1 reduced non-c-MET addicted 4T1 tumor progression dose dependently as monotherapeutic and provided additional disease reduction in combination with cisplatin. At the stromal level, OMO-1 significantly reduced neutrophil infiltration in 4T1 tumors, promoted immune activation, and enhanced cisplatin-mediated reduction of tumor-associated macrophages. OMO-1 treatment also reduced 4T1 tumor hypoxia and increased expression of pericyte markers, indicative for vascular maturation. Corroborating this finding, cisplatin delivery to the 4T1 primary tumor was enhanced upon OMO-1 treatment, increasing cisplatin DNA-adduct levels and tumor cell death. Although verification in additional cell lines is warranted, our findings provide initial evidence that TNBC patients may benefit from OMO-1 treatment, even in cases of non-c-MET addicted tumors.
format	article
author	Jonas Steenbrugge Niels Vander Elst Kristel Demeyere Olivier De Wever Niek N. Sanders Wim Van Den Broeck Eric Ciamporcero Timothy Perera Evelyne Meyer
author_facet	Jonas Steenbrugge Niels Vander Elst Kristel Demeyere Olivier De Wever Niek N. Sanders Wim Van Den Broeck Eric Ciamporcero Timothy Perera Evelyne Meyer
author_sort	Jonas Steenbrugge
title	OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer
title_short	OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer
title_full	OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer
title_fullStr	OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer
title_full_unstemmed	OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer
title_sort	omo-1 reduces progression and enhances cisplatin efficacy in a 4t1-based non-c-met addicted intraductal mouse model for triple-negative breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b9aac903f53b496da8763625e4385c99
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OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer

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