Pre-clinical research for mechanism of resistance toward MEK inhibitors in neuroblastoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Tanaka Tomoko 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (20822414)
• Co-Investigator(Kenkyū-buntansha): 東 真弓 広島大学, 医学(系)研究科(研究院), 講師 (10380453) ; 文野 誠久 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40405254) ; 田尻 達郎 九州大学, 医学(系)研究科(研究院), 教授 (80304806)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 神経芽腫 / MEK阻害剤 / YAP阻害剤

Outline of Final Research Achievements

In this study, we confirmed the efficacy of the combination of the MEK inhibitor trametinib and the YAP inhibitor CA3 against the human neuroblastoma cell line SK-N-AS. in vitro, CA3 inhibited YAP expression, stopped cell growth, and induced apoptosis. The combination of trametinib and CA3 showed a very strong synergistic effect. In experiments using mouse models of subcutaneous tumors, the combination therapy suppressed tumor growth and significantly prolonged survival. In the future, we aim to develop a protocol that can contribute to further inhibition of resistance acquisition and improvement of clinical long-term prognosis by combining the combination with surgical resection of tumors and other procedures.

Free Research Field

神経芽腫

Academic Significance and Societal Importance of the Research Achievements

再発神経芽腫は現在の集学的治療をもってしても予後不良であり、新規治療の開発が望まれている。本研究では、ヒト神経芽腫細胞株SK-N-AS に対するMEK阻害剤TrametinibとYAP阻害剤CA3の併用療法の有効性をin vitroおよびin vivoにおいて証明した。今後腫瘍の摘出など外科的治療と組み合わせることで、再発神経芽腫の長期予後改善に寄与できる最適なプロトコル作成につながっていくと考えられる。