Elucidation of the Mechanism of Action of Newly Synthesized Antitumor Compounds Against Endometrial Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09491
• 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: Shinshu University
• Principal Investigator: Yamada Yasushi 信州大学, 学術研究院医学系(医学部附属病院), 助教 (60646652)
• Co-Investigator(Kenkyū-buntansha): 塩沢 丹里 信州大学, 学術研究院医学系, 教授 (20235493) ; 竹内 穂高 信州大学, 医学部附属病院, 助教(診療) (30816351) ; 宮本 強 信州大学, 学術研究院医学系, 准教授 (70418721)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: サイクリンA / 子宮内膜癌 / 分子標的薬

Outline of Final Research Achievements

In recent years, the incidence of endometrial cancer has been significantly increasing in our country, and the development of new treatments is eagerly awaited. Upon examining the mechanisms of endometrial cancer proliferation, we found that the overexpression of cyclin A2, which promotes cell cycle progression, is a poor prognostic factor, and we considered cyclin A2 to be a suitable therapeutic target. To identify compounds with cyclin A2 transcription inhibitory activity, we screened a library of small molecule compounds and identified compound X, which inhibits both the transcription of cyclin A2 and cell proliferation. After synthesizing the modified compound X1, it was found that X1 has ten times the antitumor activity of X. This study primarily evaluated the antitumor effect and safety of this compound using a mouse model of endometrial cancer.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

これまでX1の内膜癌細胞株に対する抗腫瘍効果と、ヌードマウス皮下移植モデルでのX1の抗腫瘍効果は示して来たが、免疫不全のない子宮体癌発癌マウスモデルでの検討をしたことで、よりヒトへの投与に近い状態での抗腫瘍効果の検討が行われた。また、化合物の生体に対する安全性の評価を行うことができた。これらの結果は、今後化合物X1の臨床応用を検討するに当たり、非常に有益な情報となる。