2023 Fiscal Year Final Research Report
Development of therapeutic drug against TNBC based on mechanism of ER induction
| Project/Area Number |
21K06641
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | トリプルネガティブ乳癌 / エストロゲン受容体 / YB-1 |
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| Outline of Final Research Achievements |
YB-1 was expressed at similar levels in four subtypes of breast cancer, but phosphorylated YB-1 expression was found to be significantly higher in tumors of patients with triple negative breast cancer (TNBC) as compared with other subtypes. Inhibition of YB-1 phosphorylation (pYB-1) stabilized ERα protein. Moreover, the phosphorylated YB-1 bind to ERα protein and promoted ERα protein degradation. The combination of pYB-1 inhibitor and ERα inhibitor showed synergetic suppressive effect on TNBC growth in vitro and in vivo. The present finding demonstrated that pYB-1 is a potential therapeutic target for treatment of TNBC.
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| Free Research Field |
腫瘍生物学
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| Academic Significance and Societal Importance of the Research Achievements |
TNBCは治療標的となる因子を発現する場合が少なく、有効な治療薬の創出が必要とされている。本研究では、リン酸化YB-1標的薬はTNBCにおいてYB-1とERαの複合体形成を阻害しERαの安定性を上昇させ、タンパク質発現を上昇させることを明らかにした。さらに、動物実験においてリン酸化YB-1標的薬がERαのタンパク質発現を上昇させ、ERα標的薬に対する感受性を得ることを見出した。本研究は、HER2やERα等の標的がないTNBCの一部のサブタイプにおいてERαが標的になり得ることを示すことが出来た。
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