Investigation of crosstalk between Fanconi Anemia pathway and ATM for novel therapeutic strategies of chemoresistant ALT-positive high-risk neuroblastoma

• Project/Area Number: 24K10442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Research Institute for Clinical Oncology Saitama Cancer Center
• Principal Investigator: AKTER JESMIN 地方独立行政法人埼玉県立病院機構埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 研究員 (70795830)
• Project Period (FY): 2024-04-01 – 2028-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2027: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2026: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2025: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: Neuroblastoma / Telomere maintenance / ALT / Chemoresistance / ATM

Outline of Research at the Start

Unlimited cancer cell proliferation is achieved by maintaining telomeres via either telomerase activation or ALT (alternative lengthening of telomeres). Constitutive ATM activation in response to telomere dysfunction in ALT-positive neuroblastoma (NB) cells contributes to chemoresistance. The detailed molecular mechanism behind the chemoresistance is still unclear. By this, we will elucidate the detailed molecular mechanism of chemotherapy resistance that is thought to exist in ALT-positive NB cells, and to identify new molecular targets for overcoming chemotherapeutic drug resistance.