Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment response
Abstract Bone is the most common site of prostate cancer metastasis, leading to significant morbidity, treatment resistance, and mortality. A major challenge in understanding treatment response is the complex, bone metastatic niche. Here, we report the first patient-specific microphysiological syste...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08384-2 |
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| author | Cristina Sánchez-de-Diego Ravi Chandra Yada Nan Sethakorn Peter G. Geiger Adeline B. Ding Erika Heninger Fauzan Ahmed María Virumbrales-Muñoz Nikolett Lupsa Emmett Bartels Kacey Stewart Suzanne M. Ponik Marina N. Sharifi Joshua M. Lang David J. Beebe Sheena C. Kerr |
| author_facet | Cristina Sánchez-de-Diego Ravi Chandra Yada Nan Sethakorn Peter G. Geiger Adeline B. Ding Erika Heninger Fauzan Ahmed María Virumbrales-Muñoz Nikolett Lupsa Emmett Bartels Kacey Stewart Suzanne M. Ponik Marina N. Sharifi Joshua M. Lang David J. Beebe Sheena C. Kerr |
| author_sort | Cristina Sánchez-de-Diego |
| collection | DOAJ |
| description | Abstract Bone is the most common site of prostate cancer metastasis, leading to significant morbidity, treatment resistance, and mortality. A major challenge in understanding treatment response is the complex, bone metastatic niche. Here, we report the first patient-specific microphysiological system (MPS) to incorporate six primary human stromal cell types found in the metastatic bone niche (mesenchymal stem cells, adipocytes, osteoblasts, osteoclasts, fibroblasts, and macrophages), alongside an endothelial microvessel, and prostate tumor epithelial spheroids in an optimized media that supports their viability and phenotype. We tested two standard of care drugs, darolutamide and docetaxel, in addition to sacituzumab govitecan (SG), currently in clinical trials for prostate cancer, demonstrating that the MPS accurately replicates androgen response sensitivity and captures stromal microenvironment-mediated resistance. This advanced MPS provides a robust platform for investigating the biological mechanisms of treatment response and for identification and testing of therapeutics to advance patient-specific MPS towards personalized clinical-decision making. |
| format | Article |
| id | doaj-art-a23ac740947b430cb71651a68ebd65dd |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-a23ac740947b430cb71651a68ebd65dd2025-08-20T03:45:34ZengNature PortfolioCommunications Biology2399-36422025-07-018112210.1038/s42003-025-08384-2Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment responseCristina Sánchez-de-Diego0Ravi Chandra Yada1Nan Sethakorn2Peter G. Geiger3Adeline B. Ding4Erika Heninger5Fauzan Ahmed6María Virumbrales-Muñoz7Nikolett Lupsa8Emmett Bartels9Kacey Stewart10Suzanne M. Ponik11Marina N. Sharifi12Joshua M. Lang13David J. Beebe14Sheena C. Kerr15Carbone Cancer Center, University of WisconsinCarbone Cancer Center, University of WisconsinDepartment of Medicine, Loyola University ChicagoDepartment of Pathology & Laboratory Medicine, University of WisconsinCarbone Cancer Center, University of WisconsinCarbone Cancer Center, University of WisconsinDepartment of Pathology & Laboratory Medicine, University of WisconsinCarbone Cancer Center, University of WisconsinCarbone Cancer Center, University of WisconsinDepartment of Pathology & Laboratory Medicine, University of WisconsinDepartment of Pathology & Laboratory Medicine, University of WisconsinCarbone Cancer Center, University of WisconsinCarbone Cancer Center, University of WisconsinCarbone Cancer Center, University of WisconsinCarbone Cancer Center, University of WisconsinCarbone Cancer Center, University of WisconsinAbstract Bone is the most common site of prostate cancer metastasis, leading to significant morbidity, treatment resistance, and mortality. A major challenge in understanding treatment response is the complex, bone metastatic niche. Here, we report the first patient-specific microphysiological system (MPS) to incorporate six primary human stromal cell types found in the metastatic bone niche (mesenchymal stem cells, adipocytes, osteoblasts, osteoclasts, fibroblasts, and macrophages), alongside an endothelial microvessel, and prostate tumor epithelial spheroids in an optimized media that supports their viability and phenotype. We tested two standard of care drugs, darolutamide and docetaxel, in addition to sacituzumab govitecan (SG), currently in clinical trials for prostate cancer, demonstrating that the MPS accurately replicates androgen response sensitivity and captures stromal microenvironment-mediated resistance. This advanced MPS provides a robust platform for investigating the biological mechanisms of treatment response and for identification and testing of therapeutics to advance patient-specific MPS towards personalized clinical-decision making.https://doi.org/10.1038/s42003-025-08384-2 |
| spellingShingle | Cristina Sánchez-de-Diego Ravi Chandra Yada Nan Sethakorn Peter G. Geiger Adeline B. Ding Erika Heninger Fauzan Ahmed María Virumbrales-Muñoz Nikolett Lupsa Emmett Bartels Kacey Stewart Suzanne M. Ponik Marina N. Sharifi Joshua M. Lang David J. Beebe Sheena C. Kerr Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment response Communications Biology |
| title | Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment response |
| title_full | Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment response |
| title_fullStr | Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment response |
| title_full_unstemmed | Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment response |
| title_short | Engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient-specific treatment response |
| title_sort | engineering the bone metastatic prostate cancer niche through a microphysiological system to report patient specific treatment response |
| url | https://doi.org/10.1038/s42003-025-08384-2 |
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