The synergistic antitumor effect of combination therapy with a MEK inhibitor and YAP inhibitor on pERK-positive neuroblastoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20948
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Takemoto Masakazu 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (40964789)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 神経芽腫 / MEK阻害薬 / YAP阻害薬

Outline of Final Research Achievements

Mice were divided into two groups: a mouse model group with minimal residual disease (MRD) and a sham operation group in which only skin incisions were made without resection of the tumour, and the two groups were treated with trametinib and trametinib/CA3, respectively. The prognosis and tumour control efficacy of all four groups were investigated.
At the 4-week follow-up period, all mice in the MRD group were alive in both the trametinib monotherapy group and the trametinib/CA3 combination group; the Sham operation group showed a significant survival benefit in the trametinib/CA3 combination group.
Tumour suppression was significant in the trametinib/CA3 combination group in both the MRD and sham surgery groups. Tumour suppression was greatest in the MRD group treated with the trametinib/CA3 combination.

Free Research Field

腫瘍

Academic Significance and Societal Importance of the Research Achievements

進行神経芽腫は現在でも予後不良であり新規治療薬の開発が望まれる.我々は先行研究でMEK阻害剤トラメチニブの神経芽腫に対するin vitroおよびin vivoの治療効果を報告した.その後，臨床応用へ向けてヒトにおける腫瘍摘出後残存病変を模した微少残存病変マウスモデルを作成し，トラメチニブ/CA3を併用することで腫瘍増殖抑制期間および生存期間を更に延長できることを確認した.
トラメチニブ/CA併用療法の至適治療プロトコルをベースに，実臨床におけるトラメチニブを使用した治療プロトコルを立案するが，本邦の神経芽腫臨床試験の後療法として実臨床に支障がない現実的な治療プロトコルの策定を目指す．