2021 Fiscal Year Final Research Report
Cross-talk betwen NOTCH and YAP pathways in human intrahepatic cholangiocarcinoma growth
Project/Area Number |
19K17473
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Nara Medical University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 肝内胆管癌 |
Outline of Final Research Achievements |
Advanced intrahepatic cholangiocarcinoma is associated with poor prognosis and limited response to systemic chemotherapy. The aim of this study was to develop a new therapeutic approach through the regulation of Hippo/YAP and NOTCH signaling, which are involved in the pathogenesis of intrahepatic cholangiocarcinoma. We found that the combination of an angiotensin II blocker, which is known to inhibit YAP activation, with a selective NOTCH1 inhibitor efficiently suppressed the development of human intrahepatic cholangiocarcinoma through mechanisms such as cell growth inhibition, apoptosis induction, and angiogenesis inhibition.
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Free Research Field |
慢性肝疾患
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Academic Significance and Societal Importance of the Research Achievements |
切除不能な肝内胆管癌に対して国内外で標準治療としてゲムシタビン(GEM)+シスプラチン(CDDP)療法が位置付けられているが、しかし生存期間、奏効率ともに十分な治療効果は得られていない。そのため、肝内胆管癌に対して新たな抗癌治療戦略を考えることは急務である。本研究においてYAPおよびNOTCHの制御が肝内胆管癌の発育を効率的に抑えることを明らかにしたことで、今後の肝内胆管癌治療における新たなオプションとして臨床への応用を見据えた展開が期待できると思われる。
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