乳癌におけるSEMA3FのCDK4/6阻害剤に対する耐性メカニズムの解明

• Project/Area Number: 24K11790
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Keio University
• Principal Investigator: 永山 愛子 慶應義塾大学, 医学部(信濃町), 助教 (00573396)
• Co-Investigator(Kenkyū-buntansha): 藏本 純子 慶應義塾大学, 医学部(信濃町), 講師 (60571677) ; 林田 哲 慶應義塾大学, 医学部(信濃町), 講師 (80327543)
• Project Period (FY): 2024-04-01 – 2029-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2028: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2027: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2026: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2025: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 乳癌 / CDK4/6阻害剤 / 細胞周期

Outline of Research at the Start

CDK4/6 inhibitors improved survival in advanced breast cancer, however, the tumors eventually acquire resistance. In our previous project, we identified a novel CDK4/6 inhibitor resistant gene, SEMA3F, via the whole-genome CRISPR/Cas9 knockout screen.
SEMA3F is known to function as axon guidance but its role in breast cancer is not clear. Thus, we aim to investigate how SEMA3F confers resistance to CDK4/6 inhibitors. We plan to analyze CDK4/6 kinase activity, cell cycle, apoptosis, cell migration in SEMA3F-ko cells and its correlation with clinical response in patients’samples.