Assessment of radiation resistance in head and neck cancer with high metabolic tumor volume by using organoid culture method

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Yokohama City University
• Principal Investigator: Yabuki Kenichiro 横浜市立大学, 医学研究科, 客員講師 (50722774)
• Co-Investigator(Kenkyū-buntansha): 佐野 大佑 横浜市立大学, 医学部, 講師 (10620990) ; 上野 康晴 東京大学, 医科学研究所, 特任助教 (60375235) ; 谷口 英樹 東京大学, 医科学研究所, 教授 (70292555) ; 折舘 伸彦 横浜市立大学, 医学研究科, 教授 (90312355)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: オルガノイド培養法 / 頭頸部癌 / 腺様嚢胞癌 / 薬剤感受性試験

Outline of Final Research Achievements

Tumor specimens from surgically resected salivary adenoid cystic carcinoma (ACC) were proceeded for the preparation of patient-derived tumor xenograft (PDX) and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC derived-organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYB translocation and histological features of the original parent and PDX tumors. Lastly, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents.

Free Research Field

頭頸部癌

Academic Significance and Societal Importance of the Research Achievements

本研究成果は今後の頭頸部腺様嚢胞癌に対する病態解明や治療法の確立に資するだけでなく，頭頸部癌症例の個別化治療が実現する可能性を示したものであると思われます．特にオルガノイド培養法は新規性の高い培養法であり，他分野での応用も期待されます．