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Commun Biol. 2019 Feb 25;2:78. doi: 10.1038/s42003-019-0305-x. eCollection 2019.

A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids.

Author information

1
1Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 USA.
2
Present Address: Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, HCM City, Vietnam.
3
2Molecular Screening Shared Resource, California NanoSystems Institute, University of California, Los Angeles, CA 90095 USA.
4
3Department of Biostatistics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 USA.
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4Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 USA.
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5Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 USA.
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6Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095 USA.
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7The VA Greater Los Angeles Health Care System, Los Angeles, CA 90073 USA.
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8Department of Biological Chemistry, University of California, Los Angeles, CA 90095 USA.
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9Molecular Biology Institute, University of California, Los Angeles, CA 90095 USA.
11
10Department of Molecular and Medicinal Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 USA.

Abstract

Tumor organoids maintain cell-cell interactions, heterogeneity, microenvironment, and drug response of the sample they originate from. Thus, there is increasing interest in developing tumor organoid models for drug development and personalized medicine applications. Although organoids are in principle amenable to high-throughput screenings, progress has been hampered by technical constraints and extensive manipulations required by current methods. Here we introduce a miniaturized method that uses a simplified geometry by seeding cells around the rim of the wells (mini-rings). This allows high-throughput screenings in a format compatible with automation as shown using four patient-derived tumor organoids established from two ovarian and one peritoneal high-grade serous carcinomas and one carcinosarcoma of the ovary. Using our automated screening platform, we identified personalized responses by measuring viability, number, and size of organoids after exposure to 240 kinase inhibitors. Results are available within a week from surgery, a timeline compatible with therapeutic decision-making.

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