Development of innovative targeted therapies by essential control of HGF/MET axis in scirrhous gastric cancer treatment

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa Medical University
• Principal Investigator: YASUMOTO Kazuo 金沢医科大学, 医学部, 教授 (90262592)
• Co-Investigator(Kenkyū-buntansha): 石垣 靖人 金沢医科大学, 総合医学研究所, 教授 (20232275)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: スキルス胃癌 / 癌性腹膜炎 / 分子標的治療

Outline of Final Research Achievements

We need to address high-priority issue for the development of new target therapies of peritoneal carcinomatosisis from scirrhous gastric cancer. Our results in this study strongly suggest that HGF- and amphiregulin-induced activation of MET- and/or EGFR-mediated signaling pathways, MEK and mTOR, play important roles in the pathogenesis of peritoneal carcinomatosis in scirrhous gastric cancer. Thus, MEK and mTOR signaling pathways may be potential therapeutic targets for peritoneal carcinomatosis of scirrhous gastric cancer.
We succeeded in development of new targeted therapy for scirrhous gastric cancer, which inhibited effectively reduced ascitic fluid formation and prolonged their survival of nude mice bearing established tumors by scirrhous gastric cancer cells. We applied for a patent for this invention.

Free Research Field

臨床腫瘍学、胃癌、癌性腹膜炎、分子標的治療

Academic Significance and Societal Importance of the Research Achievements

胃癌診療において進行癌患者の1割を占めるスキルス胃癌は、食欲低下や生命の期間を規定する腹水を伴うがん性腹膜炎を高頻度に発症する。そのため治療法の開発は喫緊の重要課題である。本研究では、スキルス胃癌特有の急速進展に深く関わる癌細胞の増殖機構にスポットを当て新たな治療法開発を目指した。
本研究で、新たな治療標的となる細胞内増殖経路の2経路の同時阻害が、非常に強い抑制効果をもたらすことを見出した。腹水の貯留する進行癌症例において新たな治療法となりうる可能性が高く、今後新規治療法の確立を視野に進める方針である。