Development of the novel cancer agents targetting LSD1 for hepatocellular carcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21292
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery; Human genetics
• Research Institution: Wakayama Medical University
• Principal Investigator: Hayami Shinya 和歌山県立医科大学, 医学部, 助教 (00468290)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 分子標的治療薬 / 肝細胞癌 / 脱メチル化 / LSD1

Outline of Final Research Achievements

The aim of this study is development and clinical application of a new molecular target therapeutic drug, targeting demethylation by LSD1 (Lysine-specific demethylase 1) / KDM1A (Lysine Demethylase 1A), as a novel pathway different from the kinase inhibitor. We first performed immunohistochemical analysis using anti-LSD1 antibody. Survival analysis showed that the survival rate in LSD1-high expression group was significantly poor in five-year overall survival and recurrence-free survival. LSD1-high expression was also an independent poor prognostic factor in multivariate analysis. It has been suggested that LSD1 inhibitors may be ideal molecular targeted therapeutic agents.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究では肝細胞癌における、脱メチル化酵素LSD1の寄与について検討した。LSD1が高発現している肝細胞癌においては予後不良であることを証明し、独立した危険因子であることを証明し得た。本研究は最終的に303例という大きな症例数を有しており、かつ詳細なデータベースに基づく解析を行った点で、非常に信頼性が高く貴重な検討であると考える。今後LSD1が肝細胞癌をターゲットとした新規分子標的治療薬として、臨床応用できるようさらなる検討が必要である。