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Development of novel treatment for liver cancer with class-selective HDAC inhibitors

Research Project

Project/Area Number 18K07914
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionSapporo Medical University

Principal Investigator

Miyanishi Koji  札幌医科大学, 医学部, 准教授 (60372819)

Co-Investigator(Kenkyū-buntansha) 加藤 淳二  札幌医科大学, 医学部, 教授 (20244345)
田中 信悟  札幌医科大学, 医学部, 助教 (60561024)
菊地 尚平  札幌医科大学, 医学部, 助教 (80515792)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords肝細胞癌 / 化学療法 / ヒストン脱アセチル化酵素 / 相乗効果 / 治療 / 薬物搬送
Outline of Final Research Achievements

Histone deacetylase (HDAC) is expressed in various cancers and is involved in cancer treatment resistance. HDAC class IIa is found in hepatocellular carcinoma cells. In this study, we found that the combined use of HDAC class IIa inhibitors with lenvatinib induces a synergistic antitumor effect. Lenvatinib is thought to exert an antitumor effect by inhibition of fibroblast growth factor receptor 4 (FGFR4) . It is considered that the induction of apoptosis by the combined use of both drugs depends on the expression of FGFR4. Furthermore, the decreased expression of FGFR4 was considered to induce a synergistic effect.

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌の標準的な薬物治療には、癌細胞や血管新生因子の増殖を抑制する、レンバチニブ等の分子標的薬治療と、血管新生阻害薬と免疫チェックポイント阻害薬の併用が挙げられる。また、切除できない肝細胞癌の治療として、肝動脈化学塞栓術がある。本研究の結果は、レンバチニブの効果を増強するHDAC class IIa阻害薬を用いた新たな薬物療法が有効である可能性を示した。いずれの治療が選択すべきかについては、肝細胞癌の個数、サイズや肝機能をもとに考えられることが多いが、本研究結果はFGFR4の発現が多い肝細胞癌では本療法がより有効であることを示し、治療効果を予測できる可能性も示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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