4.8 Article

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

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SCIENCE ADVANCES
卷 7, 期 27, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abg2564

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资金

  1. IHBI ECR grant
  2. Advance Queensland (AQ) Maternity Fund Award from the Queensland Government (DSITI)
  3. Young Researcher Award from Lush (UK) [2017-YR-RoW-9]
  4. National Health and Medical Research Council (NHMRC) Peter Doherty Early Career Research Fellowship (RF) [APP1091734]
  5. John Mills Young Investigator Award from the Prostate Cancer Foundation of Australia (PCFA) [YI0715]
  6. JJ Richards & Sons via an In Vitro Excellence Research grant
  7. ARC Industrial Transformation Training Center in Additive Biomanufacturing [IC160100026]
  8. NHMRC
  9. World Cancer Foundation
  10. National Breast Cancer Foundation
  11. PCFA
  12. Movember
  13. Australian Government

向作者/读者索取更多资源

The all-human microtissue-engineered model of mineralized metastatic tissue plays a crucial role in understanding the bone tumor microenvironment and treatment response in mCRPC, with enzalutamide demonstrating better therapeutic efficacy compared to bicalutamide in a mineralized microenvironment.
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.

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