Effect of Wee1 inhibitors on human papilloma virus-related cervical cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09678
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nihon University
• Principal Investigator: IKEDA Yuji 日本大学, 医学部, 准教授 (80713453)
• Co-Investigator(Kenkyū-buntansha): 清谷 一馬 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 主任研究員 (30433642)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Wee1阻害薬 / 子宮頸癌

Outline of Final Research Achievements

In this study, we investigated the effect of a Wee1 inhibitor on cervical cancer caused by human papilloma virus (HPV). We evaluated the drug sensitivity of the Wee1 inhibitor in vivo using various cell lines including, SiHa (HPV16+, p53 wt), CaSki (HPV16+, p53 wt) C33A (HPV－, p53 mut), and LNCaP (HPV－, p53 wt) and assessed whether the combined use of a Wee1 inhibitor and cisplatin causes a synergistic effect. Accordingly, we confirmed the difference in drug sensitivity among cell lines, enhancement of the synergistic/antitumor effect of the Wee1 inhibitor and cisplatin, and occurrence of apoptosis via DNA damage in cervical cancer cell line SiHa with TP53 loss-of-function caused by HPV16. The result indicates that the most common HPV infection in cervical cancer might possibly become a biomarker, which indicates the efficacy of Wee1 inhibitors.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

本研究により、HPV16型陽性 SiHa細胞にて顕著にシスプラチンとWee1阻害薬下における細胞障害性の相乗的な増強が確認された。つまり本研究により子宮頸癌におけるWee1の細胞周期調節機序が解明され、既存の標準治療法の増強作用をもたらすWee1を標的にした子宮頸癌の新たな治療開発の一端に貢献することが予測された。特に一般臨床で施行されている放射線化学療法の条件下にてWee1阻害薬の治療増強効果が確認され、今後臨床試験を経て実臨床にこの治療法が応用される事が大きく期待される。