@article{fcafbae2f9844797a3390c61cb7e59b0,
title = "High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids",
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 = "high-content imaging, organoids, PARP inhibitor, patient-derived xenograft, prostate cancer",
author = "Nicholas Choo and Susanne Ramm and Jennii Luu and Winter, {Jean M.} and Selth, {Luke A.} and Dwyer, {Amy R.} and Mark Frydenberg and Jeremy Grummet and Shahneen Sandhu and Hickey, {Theresa E.} and Tilley, {Wayne D.} and Taylor, {Renea A.} and Risbridger, {Gail P.} and Lawrence, {Mitchell G.} and Simpson, {Kaylene J.}",
note = "Funding Information: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G. Risbridger, R. Taylor, and M. Lawrence, provision of reagents for laboratory research (Zenith Epigenetics) and other research collaborations (Pfizer, Astellas). J. Grummet, honoraria from BK Ultrasound, Biobot, Mundipharma; travel: Astellas; owner of MRI PRO Pty Ltd., an online training platform. S. Sandhu, grant funding to institution from AstraZeneca, Novartis, Amgen, Pfizer, Genentech, Merck Sharp and Dohme, Merck Serono; honoraria donated to institution from Merck Sharp and Dohme, Astra Zeneca, and Bristol Myer Squibb. All other authors have no conflicts of interest to declare. Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Health and Medical Research Council, Australia (fellowship to G.P.R. 1102752, project grants 1138242 and 1156570; ideas grant 1186647 to W.D.T.); the Department of Health and Human Services acting through the Victorian Cancer Agency (fellowships to M.G.L. MCRF18017, R.A.T. MCRF15023, CAPTIV Program); Movember & the National Breast Cancer Foundation (NBCF; Collaboration Initiative Grant to T.E.H, G.P.R, L.A.S., and W.D.T.); the US Department of Defense through the Prostate Cancer Research Program (G.P.R. W81XWH1810349; opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense); the CASS Foundation (medical science grant 7139 to M.G.L.); the Movember Foundation (Global Action Plan 1); the EJ Whitten Foundation; the Peter and Lyndy White Foundation; TissuPath Pathology; The Hospital Research Foundation (ID 2018-06-Strategic-R; T.E.H., L.A.S., W.D.T.); NBCF (fellowship IIRS-19-009 to T.E.H.); Cancer Council SA Beat Cancer Project (Early Career Cancer Research Fellowship to J.M.W.); the University of Adelaide (W.D.T.); and Flinders Health and Medical Research Institute, Flinders University (L.A.S.). L.A.S. is supported by principal cancer research fellowships awarded by the Cancer Council{\textquoteright}s Beat Cancer project on behalf of its donors, the state government through the Department of Health, and the Australian government through the Medical Research Future Fund. The Victorian Centre for Functional Genomics (K.J.S.) is funded by the Australian Cancer Research Foundation (ACRF), Phenomics Australia (PA) through funding from the Australian Government{\textquoteright}s National Collaborative Research Infrastructure Strategy (NCRIS) program, the Peter MacCallum Cancer Centre Foundation, and the University of Melbourne Research Collaborative Infrastructure Program (MCRIP). Publisher Copyright: {\textcopyright} The Author(s) 2021. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = oct,
doi = "10.1177/24725552211020668",
language = "English",
volume = "26",
pages = "1107--1124",
journal = "SLAS Discovery",
issn = "2472-5552",
publisher = "SAGE Publications Ltd",
number = "9",
}
