Comprehensive evaluation and analysis of therapeutic agents utilizing desmoid-type fibromatosis PDC

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15313
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Hamada Shunsuke 愛知県がんセンター(研究所), がん病態生理学分野, 研究員 (90747289)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: デスモイド型線維腫症 / CTNNB1変異 / Wntシグナル

Outline of Final Research Achievements

TNNB1 mutations were identified in tumor tissue from desmoid fibromatosis, and these tumor cells were isolated and cultured. The tumor cells with S45F mutation, which is considered to have a poor clinical prognosis, showed stronger nuclear migration of β-catenin than cells with other mutations. We selected candidate drugs by drug screening as novel therapeutic agents, but the inhibitory effect of each drug, including existing drugs, was relatively low in S45F mutant cells. The expression profile of Wnt signaling genes also differed from that of other mutant cells, suggesting that these genes may be involved in the unique clinical course of S45F mutant tumors, including high drug resistance and recurrence rates.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

デスモイド型線維腫症においてCTNNB1遺伝子変異はそれ自体が診断的意義を持つと同時に、その変異型が臨床的な術後再発率や薬物治療効果と相関することが報告されており、近年実臨床においても診断や治療方針の決定に有用なツールとなってきている。本研究では治療抵抗性のS45F変異型腫瘍の臨床的特徴と、細胞の分子生物学的性質について相関性が示された。今後さらに解析を進めることで、治療抵抗性の症例に対してより治療効果の高い薬剤の開発や、他の変異型を含めたより厳密な治療マーカーの確立化などが期待される。