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Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer

SIMPLE SUMMARY: A frequent disabling symptom during metastasized breast cancer is the development of ascites and pleural effusion, which is associated with poor outcomes. Malignant cells in ascites and pleural effusions derived from the primary tumor site indicate the spreading of cancer and can ser...

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Autores principales: Önder, Cansu E., Ziegler, Teresa J., Becker, Ronja, Brucker, Sara Y., Hartkopf, Andreas D., Engler, Tobias, Koch, André
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377262/
https://www.ncbi.nlm.nih.gov/pubmed/37509265
http://dx.doi.org/10.3390/cancers15143602
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author Önder, Cansu E.
Ziegler, Teresa J.
Becker, Ronja
Brucker, Sara Y.
Hartkopf, Andreas D.
Engler, Tobias
Koch, André
author_facet Önder, Cansu E.
Ziegler, Teresa J.
Becker, Ronja
Brucker, Sara Y.
Hartkopf, Andreas D.
Engler, Tobias
Koch, André
author_sort Önder, Cansu E.
collection PubMed
description SIMPLE SUMMARY: A frequent disabling symptom during metastasized breast cancer is the development of ascites and pleural effusion, which is associated with poor outcomes. Malignant cells in ascites and pleural effusions derived from the primary tumor site indicate the spreading of cancer and can serve as a model for metastatic breast cancer. Therefore, we cultured metastatic cells from six patients with ascites or pleural effusion in a three-dimensional fashion to obtain organoids. The organoids recapitulated the characteristics of metastatic samples, as shown by immunohistochemistry and mutation analysis. Drug assays of organoids were performed to assess individual responses in a personalized manner. Overall, metastatic organoid cultures derived from malignant pleural effusion and malignant ascites demonstrated in vivo-like phenotypes and drug responses. Hence, these metastatic organoids can serve as an accurate model for the investigation of breast cancer progression and therapy predictions. ABSTRACT: The poor outcome of metastasized breast cancer (BC) stresses the need for reliable personalized oncology and the significance of models recapitulating the heterogeneous nature of BC. Here, we cultured metastatic tumor cells derived from advanced BC patients with malignant ascites (MA) or malignant pleural effusion (MPE) using organoid technology. We identified the characteristics of tumor organoids by applying immunohistochemistry and mutation analysis. Tumor organoids preserved their expression patterns and hotspot mutations when compared to their original metastatic counterpart and are consequently a well-suited in vitro model for metastasized BC. We treated the tumor organoids to implement a reliable application for drug screenings of metastasized cells. Drug assays revealed that responses are not always in accord with expression patterns, pathway activation, and hotspot mutations. The discrepancy between characterization and functional testing underlines the relevance of linking IHC stainings and mutational analysis of metastasized BC with in vitro drug assays. Our metastatic BC organoids recapitulate the characteristics of their original sample derived from MA and MPE and serve as an invaluable tool that can be utilized in a preclinical setting for guiding therapy decisions.
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spelling pubmed-103772622023-07-29 Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer Önder, Cansu E. Ziegler, Teresa J. Becker, Ronja Brucker, Sara Y. Hartkopf, Andreas D. Engler, Tobias Koch, André Cancers (Basel) Article SIMPLE SUMMARY: A frequent disabling symptom during metastasized breast cancer is the development of ascites and pleural effusion, which is associated with poor outcomes. Malignant cells in ascites and pleural effusions derived from the primary tumor site indicate the spreading of cancer and can serve as a model for metastatic breast cancer. Therefore, we cultured metastatic cells from six patients with ascites or pleural effusion in a three-dimensional fashion to obtain organoids. The organoids recapitulated the characteristics of metastatic samples, as shown by immunohistochemistry and mutation analysis. Drug assays of organoids were performed to assess individual responses in a personalized manner. Overall, metastatic organoid cultures derived from malignant pleural effusion and malignant ascites demonstrated in vivo-like phenotypes and drug responses. Hence, these metastatic organoids can serve as an accurate model for the investigation of breast cancer progression and therapy predictions. ABSTRACT: The poor outcome of metastasized breast cancer (BC) stresses the need for reliable personalized oncology and the significance of models recapitulating the heterogeneous nature of BC. Here, we cultured metastatic tumor cells derived from advanced BC patients with malignant ascites (MA) or malignant pleural effusion (MPE) using organoid technology. We identified the characteristics of tumor organoids by applying immunohistochemistry and mutation analysis. Tumor organoids preserved their expression patterns and hotspot mutations when compared to their original metastatic counterpart and are consequently a well-suited in vitro model for metastasized BC. We treated the tumor organoids to implement a reliable application for drug screenings of metastasized cells. Drug assays revealed that responses are not always in accord with expression patterns, pathway activation, and hotspot mutations. The discrepancy between characterization and functional testing underlines the relevance of linking IHC stainings and mutational analysis of metastasized BC with in vitro drug assays. Our metastatic BC organoids recapitulate the characteristics of their original sample derived from MA and MPE and serve as an invaluable tool that can be utilized in a preclinical setting for guiding therapy decisions. MDPI 2023-07-13 /pmc/articles/PMC10377262/ /pubmed/37509265 http://dx.doi.org/10.3390/cancers15143602 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Önder, Cansu E.
Ziegler, Teresa J.
Becker, Ronja
Brucker, Sara Y.
Hartkopf, Andreas D.
Engler, Tobias
Koch, André
Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer
title Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer
title_full Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer
title_fullStr Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer
title_full_unstemmed Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer
title_short Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer
title_sort advancing cancer therapy predictions with patient-derived organoid models of metastatic breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377262/
https://www.ncbi.nlm.nih.gov/pubmed/37509265
http://dx.doi.org/10.3390/cancers15143602
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