Novel therapeutic strategy for hepatocellular carcinoma by farnesyltransferase inhibitor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16776
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Saga University
• Principal Investigator: Tanaka Tomokazu 佐賀大学, 医学部, 助教 (60781903)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ファルネシル転換酵素阻害薬 / NAFLD/NASH関連肝癌 / HIF-1α / ファルネシル化 / 抗炎症反応

Outline of Final Research Achievements

In recent years, hepatocellular carcinoma (HCC) caused by NAFLD/NASH has clearly increased, but there is no effective preventive method or therapeutic drug. In this study, we examined the antitumor effect of farnesyltransferase inhibitor (FTI) and its mechanism as a novel therapeutic strategy for NAFLD/NASH-related HCC. In addition to the antitumor effect observed in several HCC cell lines, FTI showed a stronger antitumor effect in an inflammation-inducing model or lipid droplet production model assuming NAFLD/NASH-related HCC, and the anti-inflammatory effect is involved in the mechanism of the action. Moreover, the antitumor effect of FTI was confirmed in animal experiment using NASH-related HCC development model mice, and our results in this study showed that FTI will be promising as a new therapeutic agent for NAFLD/NASH-related HCC.

Free Research Field

消化器癌

Academic Significance and Societal Importance of the Research Achievements

本研究の成果（FTIのNAFLD/NASH肝癌に対する抗腫瘍効果の証明とその作用機序の検討）によって、今後も増加が見込まれるNAFLD/NASH肝癌患者に対する新たな治療選択肢の一つとなり得る可能性がある。さらに、抗腫瘍効果の作用機序の一端として、NAFLD/NASH肝癌の発癌および進行過程に大きく寄与すると思われる炎症反応をFTIが制御することから、NAFLD/NASH肝癌の治療（腫瘍縮小や進行抑制）のみならず、NAFLD/NASHに対して使用することで後の発癌抑制につながる可能性がある。