Development of oral cancer therapies targeting DNA repair pathways and intracellular material transport

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K10272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Nara Medical University
• Principal Investigator: Kirita tadaaki 奈良県立医科大学, 医学部, 教授 (70201465)
• Co-Investigator(Kenkyū-buntansha): 仲川 洋介 奈良県立医科大学, 医学部, 助教 (00714875) ; 森 英一朗 奈良県立医科大学, 医学部, 准教授 (70803659)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 口腔がん / 5-FU / ATR / 細胞周期

Outline of Final Research Achievements

The anticancer agent 5-fluorouracil (5-FU) is cytotoxic and often used to treat various cancers, including oral cancer. ATR kinase is a principal kinase in the DNA damage response and is activated in response to UV- and chemotherapeutic drug-induced DNA replication stress, but its role in cellular responses to 5-FU is unclear. In this study, we examined the effect of ATR inhibition on 5-FU sensitivity of mammalian cells. Administration of 5-FU with a specific ATR inhibitor remarkably decreased cell survival, compared with 5-FU treatment combined with other major DNA repair kinase inhibitors. These findings suggest that ATR could be a potential therapeutic target in 5-FU-based chemotherapy.

Free Research Field

口腔がん治療

Academic Significance and Societal Importance of the Research Achievements

今回の研究で、細胞周期のチェックポイントを担うATR経路が、既存の抗がん剤5-FUの効果を増大させる分子標的となり得ることが明らかとなった。ATR阻害剤は、進行性固形がんの方を対象に治験が進められており、研究成果を積み重ねることで将来5-FUとATR阻害剤の併用治療が臨床現場で行われる可能性もあるのではないかと期待される。以上から、学術的にも社会的にも今回の研究成果の意義は大きいと考える。