The treatment strategy using a new Galectin-3 inhibitor for hepatocellular carcinoma and pancreatic cancer

• Project/Area Number: 18K16342
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: University of Toyama (2021); Gunma University (2018-2020)
• Principal Investigator: Igarashi Takamichi 富山大学, 学術研究部医学系, 助教 (20648472)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: Galectin-3阻害薬 / 肝細胞癌 / 膵癌

Outline of Final Research Achievements

A novel Galectin-3 inhibitor significantly suppressed the proliferative and invasive potential of hepatocellular carcinoma and pancreatic cancer cell lines in a volume-dependent manner without toxicity to normal hepatocytes. In vivo studies, intraperitoneal daily administration of Galectin-3 inhibitor suppressed the growth of subcutaneous tumors in mice with pancreatic cancer and was well tolerated. CAGE analysis showed that Galectin-3 inhibitors act in the nucleus and inhibit elements involved in DNA replication and the cell cycle. In addition, a patient-derived xenograft model of tumor tissue transplantation was successfully established in patients with intraductal papillary mucinous carcinoma and metastatic liver carcinoma.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により肝胆膵癌のみならず、他の消化器癌に対しても新規Gal-3阻害薬を用いた治療戦略の可能性に迫ることができる。また、動物実験で有効な結果が得られれば、ヒトへの応用（臨床試験や創薬）に繋がる可能性がある。加えて、他の消化器癌バイオマーカーとの関連を探索・検証することにより、消化器癌における外科学、分子細胞生物学および薬理学を繋ぐ新たな概念が生まれる。