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A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology

Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refract...

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Autores principales: Guillen, Katrin P., Fujita, Maihi, Butterfield, Andrew J., Scherer, Sandra D., Bailey, Matthew H., Chu, Zhengtao, DeRose, Yoko S., Zhao, Ling, Cortes-Sanchez, Emilio, Yang, Chieh-Hsiang, Toner, Jennifer, Wang, Guoying, Qiao, Yi, Huang, Xiaomeng, Greenland, Jeffery A., Vahrenkamp, Jeffery M., Lum, David H., Factor, Rachel E., Nelson, Edward W., Matsen, Cindy B., Poretta, Jane M., Rosenthal, Regina, Beck, Anna C., Buys, Saundra S., Vaklavas, Christos, Ward, John H., Jensen, Randy L., Jones, Kevin B., Li, Zheqi, Oesterreich, Steffi, Dobrolecki, Lacey E., Pathi, Satya S., Woo, Xing Yi, Berrett, Kristofer C., Wadsworth, Mark E., Chuang, Jeffrey H., Lewis, Michael T., Marth, Gabor T., Gertz, Jason, Varley, Katherine E., Welm, Bryan E., Welm, Alana L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882468/
https://www.ncbi.nlm.nih.gov/pubmed/35221336
http://dx.doi.org/10.1038/s43018-022-00337-6
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author Guillen, Katrin P.
Fujita, Maihi
Butterfield, Andrew J.
Scherer, Sandra D.
Bailey, Matthew H.
Chu, Zhengtao
DeRose, Yoko S.
Zhao, Ling
Cortes-Sanchez, Emilio
Yang, Chieh-Hsiang
Toner, Jennifer
Wang, Guoying
Qiao, Yi
Huang, Xiaomeng
Greenland, Jeffery A.
Vahrenkamp, Jeffery M.
Lum, David H.
Factor, Rachel E.
Nelson, Edward W.
Matsen, Cindy B.
Poretta, Jane M.
Rosenthal, Regina
Beck, Anna C.
Buys, Saundra S.
Vaklavas, Christos
Ward, John H.
Jensen, Randy L.
Jones, Kevin B.
Li, Zheqi
Oesterreich, Steffi
Dobrolecki, Lacey E.
Pathi, Satya S.
Woo, Xing Yi
Berrett, Kristofer C.
Wadsworth, Mark E.
Chuang, Jeffrey H.
Lewis, Michael T.
Marth, Gabor T.
Gertz, Jason
Varley, Katherine E.
Welm, Bryan E.
Welm, Alana L.
author_facet Guillen, Katrin P.
Fujita, Maihi
Butterfield, Andrew J.
Scherer, Sandra D.
Bailey, Matthew H.
Chu, Zhengtao
DeRose, Yoko S.
Zhao, Ling
Cortes-Sanchez, Emilio
Yang, Chieh-Hsiang
Toner, Jennifer
Wang, Guoying
Qiao, Yi
Huang, Xiaomeng
Greenland, Jeffery A.
Vahrenkamp, Jeffery M.
Lum, David H.
Factor, Rachel E.
Nelson, Edward W.
Matsen, Cindy B.
Poretta, Jane M.
Rosenthal, Regina
Beck, Anna C.
Buys, Saundra S.
Vaklavas, Christos
Ward, John H.
Jensen, Randy L.
Jones, Kevin B.
Li, Zheqi
Oesterreich, Steffi
Dobrolecki, Lacey E.
Pathi, Satya S.
Woo, Xing Yi
Berrett, Kristofer C.
Wadsworth, Mark E.
Chuang, Jeffrey H.
Lewis, Michael T.
Marth, Gabor T.
Gertz, Jason
Varley, Katherine E.
Welm, Bryan E.
Welm, Alana L.
author_sort Guillen, Katrin P.
collection PubMed
description Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer.
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spelling pubmed-88824682022-03-15 A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology Guillen, Katrin P. Fujita, Maihi Butterfield, Andrew J. Scherer, Sandra D. Bailey, Matthew H. Chu, Zhengtao DeRose, Yoko S. Zhao, Ling Cortes-Sanchez, Emilio Yang, Chieh-Hsiang Toner, Jennifer Wang, Guoying Qiao, Yi Huang, Xiaomeng Greenland, Jeffery A. Vahrenkamp, Jeffery M. Lum, David H. Factor, Rachel E. Nelson, Edward W. Matsen, Cindy B. Poretta, Jane M. Rosenthal, Regina Beck, Anna C. Buys, Saundra S. Vaklavas, Christos Ward, John H. Jensen, Randy L. Jones, Kevin B. Li, Zheqi Oesterreich, Steffi Dobrolecki, Lacey E. Pathi, Satya S. Woo, Xing Yi Berrett, Kristofer C. Wadsworth, Mark E. Chuang, Jeffrey H. Lewis, Michael T. Marth, Gabor T. Gertz, Jason Varley, Katherine E. Welm, Bryan E. Welm, Alana L. Nat Cancer Resource Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer. Nature Publishing Group US 2022-02-24 2022 /pmc/articles/PMC8882468/ /pubmed/35221336 http://dx.doi.org/10.1038/s43018-022-00337-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Resource
Guillen, Katrin P.
Fujita, Maihi
Butterfield, Andrew J.
Scherer, Sandra D.
Bailey, Matthew H.
Chu, Zhengtao
DeRose, Yoko S.
Zhao, Ling
Cortes-Sanchez, Emilio
Yang, Chieh-Hsiang
Toner, Jennifer
Wang, Guoying
Qiao, Yi
Huang, Xiaomeng
Greenland, Jeffery A.
Vahrenkamp, Jeffery M.
Lum, David H.
Factor, Rachel E.
Nelson, Edward W.
Matsen, Cindy B.
Poretta, Jane M.
Rosenthal, Regina
Beck, Anna C.
Buys, Saundra S.
Vaklavas, Christos
Ward, John H.
Jensen, Randy L.
Jones, Kevin B.
Li, Zheqi
Oesterreich, Steffi
Dobrolecki, Lacey E.
Pathi, Satya S.
Woo, Xing Yi
Berrett, Kristofer C.
Wadsworth, Mark E.
Chuang, Jeffrey H.
Lewis, Michael T.
Marth, Gabor T.
Gertz, Jason
Varley, Katherine E.
Welm, Bryan E.
Welm, Alana L.
A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology
title A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology
title_full A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology
title_fullStr A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology
title_full_unstemmed A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology
title_short A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology
title_sort human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882468/
https://www.ncbi.nlm.nih.gov/pubmed/35221336
http://dx.doi.org/10.1038/s43018-022-00337-6
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