Impact of the 3D environment of prostate cancer organoids on treatment success
October 2021
Erasmus University Medical Center, Rotterdam, Netherlands
Organoid-based studies are proving promising results in preclinical in vitro cancer research, including prostate cancer (PCa). However, experimental variability in organoid drug trials makes reproducibility difficult. For example, PCa organoids have been observed to be less affected by cabazitaxel, abiraterone and enzalutamide than corresponding single cells prior to organoid formation. Using live-cell imaging of androgen-induced androgen receptor (AR) nuclear translocation and taxane-induced tubulin stabilisation, this study therefore investigated the influence of 3D scaffolds, spatial organoid distribution and organoid size on treatment efficacy. Scaffolds delayed AR translocation and tubulin stabilisation, with Matrigel causing more delay than synthetic hydrogel and incomplete tubulin stabilisation. The effect of the drug was further attenuated the more centrally the organoids were located in the scaffold shell. In addition, cells in the core of the organoid showed a delayed treatment effect compared to cells on the periphery of the organoid, highlighting the influence of organoid size. These results indicate that the analysis of organoid responses to drugs needs to be interpreted carefully and requires specialised measurement equipment, taking into account the underlying technical aspects.
Modeling prostate cancer treatment responses in the organoid era: 3D environment impacts drug testing
Wytske M. van Weerden
Added on: 03-01-2022
[1] https://www.mdpi.com/2218-273X/11/11/1572/htm
