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

By Nhan Phan, Jenny J Hong, Bobby Tofig, Matthew Mapua, David Elashoff, Neda A Moatamed, Jin Huang, Sanaz Memarzadeh, Robert Damoiseaux, Alice Soragni

Posted 28 Jun 2017
bioRxiv DOI: 10.1101/138412 (published DOI: 10.1038/s42003-019-0305-x)

There is increasing interest in developing 3D tumor organoid models for drug development and personalized medicine applications. While tumor organoids are in principle amenable to high-throughput drug screenings, progress has been hampered by technical constraints and extensive manipulations required by current methodologies. Here, we introduce a miniaturized, fully automatable, flexible high-throughput method using a simplified geometry to rapidly establish 3D organoids from cell lines and primary tissue and robustly assay drug responses. As proof of principle, we use our mini-ring approach to establish organoids of high-grade serous tumors and one carcinosarcoma of the ovaries and screen hundreds of protein kinase compounds currently FDA-approved or in clinical development. In all cases we could identify drugs causing significant reduction in cell viability, number and size of organoids within a week from surgery, a timeline compatible with therapeutic decision making.

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