Dataset Information

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.

SUBMITTER: Choo N

PROVIDER: S-EPMC8458687 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids.

Choo Nicholas N Ramm Susanne S Luu Jennii J Winter Jean M JM Selth Luke A LA Dwyer Amy R AR Frydenberg Mark M Grummet Jeremy J Sandhu Shahneen S Hickey Theresa E TE Tilley Wayne D WD Taylor Renea A RA Risbridger Gail P GP Lawrence Mitchell G MG Simpson Kaylene J KJ

SLAS discovery : advancing life sciences R & D 20210611 9

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 P ...[more]

PMID: 34111999

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Dataset Information

High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids.

Publications

High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids.

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