Comparative analysis of tongue cancer organoids among patients identifies the heritable nature of minimal residual disease.

Autor:	Sase M; Department of Biodefense Research, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo (formerly Medical Research Institute, Tokyo Medical and Dental University [TMDU]), Tokyo 113-8510, Japan; Department of Dentistry, Oral, and Maxillofacial Surgery, Jichi Medical University, Tochigi 329-0498, Japan., Sato T; Department of Biodefense Research, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo (formerly Medical Research Institute, Tokyo Medical and Dental University [TMDU]), Tokyo 113-8510, Japan; Department of Biochemistry and Molecular Biology, Nippon Medical School Graduate School of Medicine, Tokyo 113-8603, Japan., Sato H; Department of Biodefense Research, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo (formerly Medical Research Institute, Tokyo Medical and Dental University [TMDU]), Tokyo 113-8510, Japan; Department of Dentistry, Oral, and Maxillofacial Surgery, Jichi Medical University, Tochigi 329-0498, Japan., Miya F; Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; Center for Medical Genetics, Keio University School of Medicine, Tokyo 160-8582, Japan., Zhang S; Research Institute for Biomedical Science, Tokyo University of Science, Chiba 278-0022, Japan., Haeno H; Research Institute for Biomedical Science, Tokyo University of Science, Chiba 278-0022, Japan., Kajita M; Department of Biodefense Research, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo (formerly Medical Research Institute, Tokyo Medical and Dental University [TMDU]), Tokyo 113-8510, Japan., Noguchi T; Department of Dentistry, Oral, and Maxillofacial Surgery, Jichi Medical University, Tochigi 329-0498, Japan., Mori Y; Department of Dentistry, Oral, and Maxillofacial Surgery, Jichi Medical University, Tochigi 329-0498, Japan., Ohteki T; Department of Biodefense Research, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo (formerly Medical Research Institute, Tokyo Medical and Dental University [TMDU]), Tokyo 113-8510, Japan. Electronic address: ohteki.bre@mri.tmd.ac.jp.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Nov 02. Date of Electronic Publication: 2024 Nov 02.
DOI:	10.1016/j.devcel.2024.10.007
Abstrakt:	The relapse of tongue cancer (TC) after chemotherapy is caused by minimal residual disease (MRD), which is a few remaining cancer cells after chemotherapy. To understand the mechanism of MRD in TC, we created a library of TC organoids (TCOs) from 28 untreated TC patients at diverse ages and cancer stages. These TCOs reproduced the primary TC tissues both in vitro and in a xenograft model, and several TCO lines survived after cisplatin treatment (chemo-resistant TCOs). Of note, the chemo-resistant TCOs showed "heritable" embryonic diapause-like features before treatment and activation of the autophagy and cholesterol biosynthetic pathways. Importantly, inhibiting these pathways with specific inhibitors converted the chemo-resistant TCOs into chemo-sensitive TCOs. Conversely, autophagy activation with mTOR inhibitors conferred chemo-resistance on the chemo-sensitive TCOs. This unique model provides insights into the mechanism of MRD formation in TCs, leading to effective therapeutic approaches to reduce the recurrence of TC. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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