TY - JOUR
T1 - In vitro engineering of a bone metastases model allows for study of the effects of antiandrogen therapies in advanced prostate cancer
AU - Bock, Nathalie
AU - Kryza, Thomas
AU - Shokoohmand, Ali
AU - Röhl, Joan
AU - Ravichandran, Akhilandeshwari
AU - Wille, Marie Luise
AU - Nelson, Colleen C.
AU - Hutmacher, Dietmar W.
AU - Clements, Judith A.
PY - 2021/6/30
Y1 - 2021/6/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85109044317&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abg2564
DO - 10.1126/sciadv.abg2564
M3 - Article
C2 - 34193425
AN - SCOPUS:85109044317
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 27
M1 - eabg2564
ER -
