Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells

Takashi Kijima, Hiroshi Nakagawa, Masataka Shimonosono, Prasanna M. Chandramouleeswaran, Takeo Hara, Varun Sahu, Yuta Kasagi, Osamu Kikuchi, Koji Tanaka, Véronique Giroux,

Cellular and Molecular Gastroenterology and Hepatology · 2018 · 156 citations · 37 references

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Abstract

Background & Aims: . We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods: . Results: = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. Conclusions: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.

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