Development of novel cancer prevention strategy by the enhancement of RB family proteins

• Project/Area Number: 18K10028
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Sowa Yoshihiro 京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (70315935)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: RBファミリー / cell-basedスクリーニング / ドラッグ・リパーパシング / RB非依存 / p107 / p130 / がん / 予防 / スクリーニング

Outline of Final Research Achievements

Cell-based screening using RB-deficient human cancer cells revealed that several compounds inhibited growth in an RB-independent manner. Five of the compounds exhibited RB-independent G1 arrest, two of which were approved drugs. We also confirmed the contribution of the RB family to the RB-independent G1 arrest ability of these five compounds.
For each of the two approved drugs, we also found that another drug compound with similar pharmacological activity also had RB-independent G1 arrest activity.
Thus, it was suggested that each of the known pharmacological activities of these two approved drug compounds also exhibited RB-independent G1 arrest ability.

Academic Significance and Societal Importance of the Research Achievements

報告者らは従来、「RB再活性化」戦略に基づいたがんの予防法の研究・開発を実施してきたが、この戦略はRBが変異した一部のがんに対しては無力であった。そこでRBと同様の機能を有するp107及びp130の“RBファミリー”に着目し、RB非依存的G1期停止能を有する化合物を探索した。その成果として、既存の医薬品化合物が見いだされてきたことは、学術的には、既知の薬理活性とRB非依存的G1期停止機構の関与を示唆するものとして、また社会的には、既存医薬品のドラッグ・リパーパシングによる開発の迅速化としての意義がある。