| Project/Area Number |
17K09871
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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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| Research Field |
Endocrinology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | エストロゲン / ホルモン療法 / 乳癌 / 分子標的薬 / MCF-7 / mTOR阻害薬 / CDK4/6阻害薬 / ホルモン療法耐性 / MCF-7細胞 / T47D細胞 / シグナル伝達 / エピゲノム制御 / 乳がん / 癌幹細胞性 |
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| Outline of Final Research Achievements |
Recently, many kinds of new molecular target drugs have been developed for metastatic and advanced breast cancer. However, presently the acquiring of drug-resistance is serious problem, and more useful therapeutic strategy such as procedure or combination of these new drugs is strongly desired. To address this purpose, we have established various molecular target drug-resistant breast cancer cell lines, and analyzed the plasticity of their driver signals, and explored the mechanism of drug resistance. The growth of hormonal therapy resistant breast cancer cells was strongly dependent to intracellular phosphorylation signaling pathway, such as PI3K/Akt/mTOR pathway. Addition of inhibitor of this pathway such as everolimus indicated the driver pathway shifted to MAPK pathway-dependent. Although CDK4/6 inhibitor was eligible for many drug resistant cell lines, different mechanisms were involved in CDK4/6 inhibitor resistance.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、進行転移再発乳癌の治療、克服のために多くの新規分子標的治療薬が登場している。しかし、その耐性獲得が大きな問題となっており、治療薬の順序、各種薬剤併用など、より有効な治療戦略の構築が喫緊の課題である。そのためには各々の耐性の機序の理解が必要であり、それはひいては乳癌増殖進展のメカニズムの解明にもつながり、また臨床的にも大きな貢献が期待できる。各種分子標的薬耐性獲得時の乳癌ドライバーシグナルの可塑性に関する本研究結果はこの点において大きく貢献できるものと思われる。
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