| Project/Area Number |
16K19905
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Sakura Anna 聖マリアンナ医科大学, 医学研究科, 研究技術員 (80626698)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 乳癌 / BRCA1 / NfkBシグナリング / Bortezomib / 卵巣癌 / 分子標的治療 / NF-kBシグナリング / 癌 |
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| Outline of Final Research Achievements |
Basal-like breast cancer, a subtype of breast cancer is associated with BRCA1 dysfunction. Basal-like breast cancer is linked to poorer clinical outcome, therefore effective treatment options for this subtype is desired. Recent reports have revealed that NFkB signaling is upregulated in breast cancer with BRCA1 mutation. We hypothesized that basal-like breast cancer with BRCA1 dysfunction could be sensitive to Bortezomib, a NFkB inhibitor.
Indeed, we have revealed that cancer cell lines with BRCA1 dysfunction due to both mutation and reduced expression displayed NFkB upregulation. Also, cells with BRCA1 dysfunction are sensitive to Bortezomib through NFkB inhibition. The last series of experiments using clinical samples showed reproducible results, suggesting that Bortezomib could be a reasonable therapeutic option for basal-like breast cancer with BRCA1 dysfunction. We have been preparing a manuscript to preset our data as a scientific paper.
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| Academic Significance and Societal Importance of the Research Achievements |
Basal-like乳癌は予後不良と関連があり効果的治療方法の確立が重要である。効果的治療方法は、腫瘍だけに効果があること（選択性）と、安全性の確立された既存の薬剤で実現することが望ましい。本研究の結果により、BRCA1機能不全細胞ではNFkB経路がoncogene addictionを起こしていることを証明した。これはNFkB阻害薬がBRCA1機能不全細胞を選択的に死滅させるということである。そして本研究で用いたBortezomibは多発性骨髄腫の治療ですでに用いられている安全性の確立された薬剤である。これらの点で実用性に富んでいると考えられる。
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