Molecule target for treatment and companion diagnostic tool of peritoneal dissemination in gastric cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04281
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: KODERA Yasuhiro 名古屋大学, 医学系研究科, 教授 (10345879)
• Co-Investigator(Kenkyū-buntansha): 神田 光郎 名古屋大学, 医学系研究科, 講師 (00644668) ; 林 真路 名古屋大学, 医学部附属病院, 病院講師 (70755503) ; 田中 千恵 名古屋大学, 医学部附属病院, 病院講師 (50589786) ; 小林 大介 名古屋大学, 医学部附属病院, 病院講師 (30635595)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 胃癌 / 腹膜播種 / 分子標的治療

Outline of Final Research Achievements

Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The pathophysiology and thus targets for treatment are unknown. Synaptotagmin XIII (SYT13) was expressed in patients with peritoneal recurrence of gastric cancer. Inhibition of SYT13 expression in gastric cancer cell lines was associated with decreased invasion and migration ability of the cells. In vivo experiments using a mouse xenograft model of gastric cancer showed that intraperitoneal administration of SYT13-specific small interfering RNA or antibodies significantly inhibited the growth of peritoneal nodules and prolonged survival. SYT13 expression in primary gastric cancer tissues or ascites fluids had diagnostic potential both in the detection and prediction of peritoneal metastasis of gastric cancer. SYT13 may also be a promising target for the treatment of peritoneal metastasis of gastric cancer.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

胃癌において腹膜播種は高頻度な転移再発形式であるにもかかわらず、これを制御しうる分子標的治療薬も精度の高い診断マーカーも発展途上にある。本研究の成果をSYT13阻害薬の創薬と診断キットの開発へとつなげることにより「SYT13発現を評価し、高発現症例に対してはSYT13阻害薬による治療を行う」、というPrecision medicineが実現できる。将来的に、SYT13阻害薬は、胃癌のみならず腹膜播種を高頻度に起こす膵癌、卵巣癌などの他癌種に応用できる可能性も有する。