| Project/Area Number |
16K10474
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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 |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
Takahashi Maiko 慶應義塾大学, 医学部(信濃町), 助教 (50348661)
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| Co-Investigator(Kenkyū-buntansha) |
関 朋子 慶應義塾大学, 医学部(信濃町), 助教 (70528900)
林田 哲 慶應義塾大学, 医学部(信濃町), 講師 (80327543)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 乳癌 / ESR1 / 遺伝子変異 / CDK4/6阻害薬 / 乳がん / エストロゲン受容体 / 内分泌療法 / CDK4/6阻害剤 |
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| Outline of Final Research Achievements |
In ER-positive advanced breast cancer, ESR1 gene mutation is found in 32%, which is considered to be one of the mechanisms for endocrine treatment resistance. In this study, mutations were found in 16 of 22 (64%) relapsed metastatic biopsy specimens, of which 7 were treated with aromatase inhibitors. Furthermore, among the mutations of exon 8, three ESR1 mutant genes of Leu536Arg, Tyr537Ser, and Asp538Gly were introduced into MCF7 to prepare mutant clones, and functional analysis was performed. As a result, in the ESR1 mutant cell line, TAM had little effect, and in the combination of FUL + PAL, the RB-E2F1 pathway was most efficiently blocked and cell cycle arrest was observed.
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| Academic Significance and Societal Importance of the Research Achievements |
転移巣におけるER遺伝子変異についての研究は、欧米を中心に盛んに行われているが、本邦におけるまとまったデータは存在しない。また、内分泌治療耐性との関係を中心に研究がなされており、本研究で取り上げるCDK4/6阻害剤との関係性についての基礎・臨床データは報告が認められていない。さらに、バイオマーカーとしての有用性が示されれば、高額な薬剤費が予想されるCDK4/6阻害剤の使用に一定の根拠を示すことができ、学術的な成果のみならず、医療経済的なインパクトも高いと考えられる。
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