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Cancer Sci. 2018 Oct 21. doi: 10.1111/cas.13843. [Epub ahead of print]

High-throughput screening in colorectal cancer tissue-originated spheroids.

Author information

1
Department of Clinical Bio-resource Research and Development, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
2
Department of Biochemistry, Osaka International Cancer Institute, Osaka, Japan.
3
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
4
Project for Development of Innovative Research on Cancer Therapeutics, Cancer Precision Medicine Center, Tokyo, Japan.
5
Department of Molecular and Medical Genetics, Osaka International Cancer Institute, Osaka, Japan.
6
Department of Thoracic Surgery, Osaka International Cancer Institute, Osaka, Japan.
7
Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
8
Department of Gastrointestinal Surgery, Osaka International Cancer Institute, Osaka, Japan.
9
Animal Models of Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
10
Laboratory of Cell Cultures, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.

Abstract

Patient-derived cancer organoid culture is an important live material that reflects clinical heterogeneity. However, the limited amount of organoids available for each case as well as the considerable amount of time and cost to expand in vitro makes it impractical to perform high-throughput drug screening using organoid cultures from multiple patients. Here, we report an advanced system for the high-throughput screening of 2427 drugs using the cancer tissue-originated spheroid (CTOS) method. In this system, we apply the CTOS method in an ex vivo platform from xenograft tumors, using machines to handle CTOS and reagents, and testing a CTOS reference panel of multiple CTOS lines for the hit drugs. CTOS passages in xenograft tumors resulted in minimal changes of morphological and genomic status, and xenograft tumor generation efficiently expanded the number of CTOS to evaluate multiple drugs. Our panel of colorectal cancer CTOS lines exhibited diverse sensitivities to the hit compounds, demonstrating the usefulness of this system for investigating highly heterogeneous disease.

KEYWORDS:

3D culture; cancer; heterogeneity; high throughput screening; organoid

PMID:
30343529
DOI:
10.1111/cas.13843
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