Sánchez-de-Diego Cristina, Yada Ravi Chandra, Sethakorn Nan, Geiger Peter G, Ding Adeline B, Heninger Erika, Ahmed Fauzan, Virumbrales-Muñoz María, Lupsa Nikolett, Bartels Emmett, Stewart Kacey, Ponik Suzanne M, Sharifi Marina N, Lang Joshua M, Beebe David J, Kerr Sheena C
Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.
Department of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
Commun Biol. 2025 Jul 1;8(1):961. doi: 10.1038/s42003-025-08384-2.
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.
骨骼是前列腺癌转移最常见的部位，会导致严重的发病率、治疗抵抗和死亡率。理解治疗反应的一个主要挑战是复杂的骨转移微环境。在此，我们报告首个患者特异性微生理系统（MPS），该系统整合了在骨转移微环境中发现的六种原代人基质细胞类型（间充质干细胞、脂肪细胞、成骨细胞、破骨细胞、成纤维细胞和巨噬细胞），以及一个内皮微血管，和前列腺肿瘤上皮球体，置于一种优化培养基中，以维持它们的活力和表型。除了目前正在进行前列腺癌临床试验的戈沙妥珠单抗（SG）外，我们还测试了两种标准护理药物，达罗他胺和多西他赛，证明该MPS能准确复制雄激素反应敏感性，并捕捉基质微环境介导的耐药性。这种先进的MPS为研究治疗反应的生物学机制以及识别和测试治疗药物提供了一个强大的平台，以推动患者特异性MPS走向个性化临床决策。
