Eradication of the interaction of adenoid cystic carcinoma of the salivary gland and cancer-associated neurons in the tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09873
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Yokohama City University
• Principal Investigator: TAKAHASHI Hideaki 横浜市立大学, 附属病院, 助教 (50727196)
• Co-Investigator(Kenkyū-buntansha): 佐野 大佑 横浜市立大学, 医学部, 准教授 (10620990) ; 折舘 伸彦 横浜市立大学, 医学研究科, 教授 (90312355)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 腫瘍神経学 / 頭頸部癌 / 唾液腺癌 / がん微小環境 / 腺様嚢胞癌

Outline of Final Research Achievements

We established patient-derived xenograft (PDX) model, cancer organoids, and PDX-derived organoids of salivary gland cancer (SGC) including adenoid cystic carcinoma (ACC) for the first time in the world. We also demonstrated that these models are similar to the original tumor in terms of histological and molecular pathological findings, and useful as preclinical models of the anticancer treatment. Moreover, we performed immunohistological analysis using the clinical specimens and found that patients with increased density sympathetic and parasympathetic nerves had worse prognosis than those without axonogenesis. These results suggest that the treatment targeting cancer-associated neurons in patients with SGC including ACC is novel and promising, and we made a significant evolution in cancer neuroscience.

Free Research Field

耳鼻咽喉科頭頸部外科学

Academic Significance and Societal Importance of the Research Achievements

本研究では，従来成功していなかった唾液腺癌の患者由来異種移植モデルや唾液腺癌オルガノイド培養技術を唾液腺腺様嚢胞癌を初めとする多様な組織型の唾液腺癌において確立し，薬効評価に有用であることを示した。こうしたモデルは癌微小環境を標的とした新しい治療法の開発を可能とする。本研究は唾液腺癌の昨今の新規治療の開発を理論的に支持しつつ，新たな有望な薬剤をスクリーニングし，臨床試験への橋渡しをするトランスレーショナルな役割も担う重要な研究であった。