In vitro engineering of a bone metastases model allows for study of the effects of antiandrogen therapies in advanced prostate cancer

Nathalie Bock, Thomas Kryza, Ali Shokoohmand, Joan Röhl, Akhilandeshwari Ravichandran, Marie Luise Wille, Colleen C. Nelson, Dietmar W. Hutmacher*, Judith A. Clements

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

While androgen-targeted therapies are routinely used in advanced prostate cancer (PCa), their effect is poorly understood in treating bone metastatic lesions and ultimately results in the development of metastatic castrate resistant prostate cancer (mCRPC). Here, we used an all-human microtissue-engineered model of mineralized metastatic tissue combining human osteoprogenitor cells, 3D printing and prostate cancer cells, to assess the effects of the antiandrogens, bicalutamide, and enzalutamide in this microenvironment. We demonstrate that cancer/ bone stroma interactions and antiandrogens drive cancer progression in a mineralized microenvironment. Probing the bone microenvironment with enzalutamide led to stronger cancer cell adaptive responses and osteomimicry than bicalutamide. Enzalutamide presented with better treatment response, in line with enzalutamide delaying time to bone-related events and enzalutamide extending survival in mCRPC. The all-human microtissue-engineered model of mineralized metastatic tissue presented here represents a substantial advance to dissect the role of the bone tumor microenvironment and responses to therapies for mCPRC.

Original languageEnglish
Article numbereabg2564
JournalScience Advances
Volume7
Issue number27
DOIs
Publication statusPublished - 30 Jun 2021
Externally publishedYes

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