Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/131449
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Type: | Journal article |
Title: | High-throughput imaging assay for drug screening of 3D prostate cancer organoids |
Author: | Choo, N. Ramm, S. Luu, J. Winter, J.M. Selth, L.A. Dwyer, A.R. Frydenberg, M. Grummet, J. Sandhu, S. Hickey, T.E. Tilley, W.D. Taylor, R.A. Risbridger, G.P. Lawrence, M.G. Simpson, K.J. |
Citation: | SLAS Discovery, 2021; 26(9):1107-1124 |
Publisher: | SAGE Publications |
Issue Date: | 2021 |
ISSN: | 2472-5552 2472-5560 |
Statement of Responsibility: | Nicholas Choo, Susanne Ramm, Jennii Luu, Jean M. Winter, Luke A. Selth, Amy R. Dwyer … et al. |
Abstract: | New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging-based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer. |
Keywords: | PARP inhibitor high-content imaging organoids patient-derived xenograft prostate cancer |
Description: | First Published June 11, 2021 |
Rights: | © The Author(s) 2021. Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) |
DOI: | 10.1177/24725552211020668 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1102752 http://purl.org/au-research/grants/nhmrc/1138242 http://purl.org/au-research/grants/nhmrc/1156570 http://purl.org/au-research/grants/nhmrc/1186647 |
Published version: | http://dx.doi.org/10.1177/24725552211020668 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
Files in This Item:
File | Description | Size | Format | |
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hdl_131449.pdf | Published version | 7.8 MB | Adobe PDF | View/Open |
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