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Article

Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing

1
Department of Urology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
2
Department of Medical Oncology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
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Cancer Treatment Screening Facility, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
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Department of Neurology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
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Department of Pathology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Prakash Kulkarni
Biomolecules 2021, 11(11), 1572; https://doi.org/10.3390/biom11111572
Received: 23 September 2021 / Revised: 19 October 2021 / Accepted: 20 October 2021 / Published: 22 October 2021
Organoid-based studies have revolutionized in vitro preclinical research and hold great promise for the cancer research field, including prostate cancer (PCa). However, experimental variability in organoid drug testing complicates reproducibility. For example, we observed PCa organoids to be less affected by cabazitaxel, abiraterone and enzalutamide as compared to corresponding single cells prior to organoid assembly. We hypothesized that three-dimensional (3D) organoid organization and the use of various 3D scaffolds impact treatment efficacy. Live-cell imaging of androgen-induced androgen receptor (AR) nuclear translocation and taxane-induced tubulin stabilization was used to investigate the impact of 3D scaffolds, spatial organoid distribution and organoid size on treatment effect. Scaffolds delayed AR translocation and tubulin stabilization, with Matrigel causing a more pronounced delay than synthetic hydrogel as well as incomplete tubulin stabilization. Drug effect was further attenuated the more centrally organoids were located in the scaffold dome. Moreover, cells in the organoid core revealed a delayed treatment effect compared to cells in the organoid periphery, underscoring the impact of organoid size. These findings indicate that analysis of organoid drug responses needs careful interpretation and requires dedicated read-outs with consideration of underlying technical aspects. View Full-Text
Keywords: prostate cancer; CRPC; organoid; 3D cell culture; preclinical models; live-cell imaging; scaffold; drug testing; cell viability prostate cancer; CRPC; organoid; 3D cell culture; preclinical models; live-cell imaging; scaffold; drug testing; cell viability
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MDPI and ACS Style

Van Hemelryk, A.; Mout, L.; Erkens-Schulze, S.; French, P.J.; van Weerden, W.M.; van Royen, M.E. Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing. Biomolecules 2021, 11, 1572. https://doi.org/10.3390/biom11111572

AMA Style

Van Hemelryk A, Mout L, Erkens-Schulze S, French PJ, van Weerden WM, van Royen ME. Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing. Biomolecules. 2021; 11(11):1572. https://doi.org/10.3390/biom11111572

Chicago/Turabian Style

Van Hemelryk, Annelies, Lisanne Mout, Sigrun Erkens-Schulze, Pim J. French, Wytske M. van Weerden, and Martin E. van Royen. 2021. "Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing" Biomolecules 11, no. 11: 1572. https://doi.org/10.3390/biom11111572

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