Novel therapeutic strategy for scirrhous gastric cancer using farnesyltransferase inhibitor

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16568
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Saga University
• Principal Investigator: Tanaka Tomokazu 佐賀大学, 医学部, 助教 (60781903)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ファルネシル転換酵素阻害薬 / HIF-1α / 腹膜播種 / 胃癌

Outline of Final Research Achievements

Scirrhous gastric cancer causing peritoneal dissemination frequently has extremely high malignant potential and resistance to treatment, therefore the development of new treatment for scirrhous gastric cancer is still desirable. In this study, we examined the anti-tumor effect of farnesyltransferase inhibitor (FTI) and its mechanism of action as a novel therapeutic strategy for scirrhous gastric cancer. FTI suppressed proliferation and migration of gastric cancer cells. Of note, FTI showed stronger anti-tumor effect on gastric cancer cells with HIF1-α high expression (HIF1-α high expression = high malignant potential). The same results were verified in animal experiments. As the mechanism of anti-tumor effect, FTI inhibited HIF1-α expression, and also suppressed mTOR pathway (a kind of signal transduction pathway involved in cancer growth) and the production of reactive oxygen species.

Free Research Field

消化器癌

Academic Significance and Societal Importance of the Research Achievements

本研究の成果（FTIのHIF1-α高発現胃癌細胞に対する抗腫瘍効果）によって、難治性転移様式である胃癌腹膜播種を発症した患者に対する新たな治療方法の選択肢となり得る可能性がある。また、腹膜播種を高率に発症するような高悪性度のHIF1-α高発現胃癌細胞にこそ治療効果が期待でき、腹膜播種再発の予防としての効果も期待できる。さらには、HIF1-α高発現は、ほとんどの固形癌に共通する高悪性度の指標であることから、FTIの治療効果は胃癌細胞のみならず、HIF1-α高発現であれば他の固形癌においても治療効果が期待できる可能性がある。