Studies on thyorid cancer pathogenesis using mouse models

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09028
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Nagasaki University
• Principal Investigator: NAGAYAMA Yuji 長崎大学, 原爆後障害医療研究所, 教授 (30274632)
• Co-Investigator(Kenkyū-buntansha): 蔵重 智美 長崎大学, 原爆後障害医療研究所, 客員研究員 (60568955) ; 嶋村 美加 長崎大学, 原爆後障害医療研究所, 助教 (90736406)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 甲状腺がん / TSH受容体 / オートファジー / インバースアゴニスト

Outline of Final Research Achievements

Thyroid cancer is the most common endocrine cancer and has been on the increase worldwide in recent years. Animal models are useful for understanding the pathogenesis of thyroid cancer and for research on the development of new treatment methods. In this study, using the mouse model that faithfully recapitulates the pathogenesis of human thyroid cancer that we have recently established, we investigated (i) the possibility of treatment with antibodies and small molecules that have a reverse agonist effect, (ii) the mechanism of action of kinase inhibitors is mainly inhibition of angiogenesis, (iii) the physiological activity of autophagy is related to (iii) physiological activity of autophagy is important for thyroid cell survival and maintenance of homeostasis, and although autophagy deficiency itself does not promote thyroid carcinogenesis, deficiency of autophagy promotes the development of thyroid cancer caused by mutant BRAF.

Free Research Field

甲状腺学

Academic Significance and Societal Importance of the Research Achievements

本研究は，世界的に増加傾向にあり，放射線での誘発がチェルノブイリから福島まで問題となっている甲状腺がんの新規治療法として逆作動薬（抗体及び低分子化合物）が有効であること，最近導入されたキナーゼ阻害剤の作用機序が実は主に血管新生阻害であること，オートファジーが甲状腺では腫瘍抑制的に作用していることを新規に見出したもので，甲状腺がんの病態から現状の治療法の作用機序，さらには将来の新規治療薬までを幅広く網羅した研究であり，甲状腺腫瘍学の進展に貢献すること大であると考える．