Stemness as a target for anti-cancer drug development

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03151
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Yamaguchi University
• Principal Investigator: Ohama Takashi 山口大学, 共同獣医学部, 准教授 (50579018)
• Co-Investigator(Kenkyū-buntansha): 大松 勉 東京農工大学, 農学部, 准教授 (60455392)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Protein Phosphatase 2A / がん幹細胞

Outline of Final Research Achievements

Recently, the importance of "cancer stem cells" as a cause of cancer recurrence, metastasis, and resistance to treatment has become clear, and drug discovery targeting these cells has attracted attention. In this study, we focused on the protein phosphatase PP2A and its inhibitor protein SET to elucidate the molecular mechanisms by which cancer stem cells maintain their stemness, and to analyze the possibility of novel drug discovery strategies targeting the protein-protein interaction between SET and PP2A. As a result, they elucidated the molecular mechanism by which SET expression is upregulated in cancer and identified small molecule compounds that dissociate the binding between SET and PP2A. A series of research results were published in three original papers during the project period, and two more research projects are currently in preparation for publication.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、がん幹細胞の幹細胞性維持機構を脱リン酸化酵素の活性阻害機構の解明を通して明らかにするものである。リン酸化酵素キナーゼと比較して脱リン酸化酵素ホスファターゼの研究は遅れており、キナーゼ阻害剤は分子標的抗がん剤として幅広く用いられているが、同じベクトルの作用を示すホスファターゼ活性化剤は、未だに上市されていない。ホスファターゼ活性化薬は、キナーゼ阻害剤との相加・相乗効果や、キナーゼ阻害剤に抵抗性または耐性を獲得した症例に対する効果が期待できる。