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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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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.
Keywords
breast cancer, cancer microenvironment, cancer models, targeted therapies

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MLA
Steenbrugge, Jonas, et al. “OMO-1 Reduces Progression and Enhances Cisplatin Efficacy in a 4T1-Based Non-c-MET Addicted Intraductal Mouse Model for Triple-Negative Breast Cancer.” NPJ BREAST CANCER, vol. 7, no. 1, 2021, doi:10.1038/s41523-021-00234-8.
APA
Steenbrugge, J., Vander Elst, N., Demeyere, K., De Wever, O., Sanders, N., Van Den Broeck, W., … Meyer, E. (2021). OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer. NPJ BREAST CANCER, 7(1). https://doi.org/10.1038/s41523-021-00234-8
Chicago author-date
Steenbrugge, Jonas, Niels Vander Elst, Kristel Demeyere, Olivier De Wever, Niek Sanders, Wim Van Den Broeck, Eric Ciamporcero, Timothy Perera, and Evelyne Meyer. 2021. “OMO-1 Reduces Progression and Enhances Cisplatin Efficacy in a 4T1-Based Non-c-MET Addicted Intraductal Mouse Model for Triple-Negative Breast Cancer.” NPJ BREAST CANCER 7 (1). https://doi.org/10.1038/s41523-021-00234-8.
Chicago author-date (all authors)
Steenbrugge, Jonas, Niels Vander Elst, Kristel Demeyere, Olivier De Wever, Niek Sanders, Wim Van Den Broeck, Eric Ciamporcero, Timothy Perera, and Evelyne Meyer. 2021. “OMO-1 Reduces Progression and Enhances Cisplatin Efficacy in a 4T1-Based Non-c-MET Addicted Intraductal Mouse Model for Triple-Negative Breast Cancer.” NPJ BREAST CANCER 7 (1). doi:10.1038/s41523-021-00234-8.
Vancouver
1.
Steenbrugge J, Vander Elst N, Demeyere K, De Wever O, Sanders N, Van Den Broeck W, et al. OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer. NPJ BREAST CANCER. 2021;7(1).
IEEE
[1]
J. Steenbrugge et al., “OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer,” NPJ BREAST CANCER, vol. 7, no. 1, 2021.
@article{8701324,
  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.}},
  articleno    = {{27}},
  author       = {{Steenbrugge, Jonas and Vander Elst, Niels and Demeyere, Kristel and De Wever, Olivier and Sanders, Niek and Van Den Broeck, Wim and Ciamporcero, Eric and Perera, Timothy and Meyer, Evelyne}},
  issn         = {{2374-4677}},
  journal      = {{NPJ BREAST CANCER}},
  keywords     = {{breast cancer,cancer microenvironment,cancer models,targeted therapies}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{14}},
  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}},
  url          = {{http://dx.doi.org/10.1038/s41523-021-00234-8}},
  volume       = {{7}},
  year         = {{2021}},
}

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