Clinicopathological and molecular biological characteristics of ovarian cancer associated with response to statins for dyslipidemia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09652
• 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: Keio University
• Principal Investigator: Kobayashi Yusuke 慶應義塾大学, 医学部(信濃町), 専任講師 (10439763)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 卵巣癌 / ドラッグリポジショニング / スタチン / 奏効予測マーカー

Outline of Final Research Achievements

A basic study was conducted to apply the dyslipidaemic drug statin as a therapeutic agent for ovarian cancer, with a view to introducing it into clinical practice. Statins showed an inhibitory effect on cell proliferation in existing ovarian cancer cell lines, particularly in serous and clear cell carcinoma cell lines. Pearson's product-moment correlation coefficients were calculated from gene expression and statin-treated cell viability by microarray analysis, and VDAC1 and LDLRAP1 gene expression were found to be predictive markers of statin response. Furthermore, when statin response in clinical samples was examined by growth inhibition rate, it was found that statin response was particularly observed in serous and clear cell carcinoma cases, with some cases showing comparable growth inhibition rates compared to standard ovarian cancer treatment agents.

Free Research Field

婦人科腫瘍学、遺伝腫瘍学、新規創薬

Academic Significance and Societal Importance of the Research Achievements

脂質異常症治療薬スタチンの抗腫瘍効果は様々な癌種で報告されており今後の臨床への還元が期待されているものの、他癌種での臨床試験では奏効予測に基づく症例選択が出来ていないため有望な結果が得られていないのが現状である。卵巣癌に対しては本研究において樹立したバイオマーカーVDAC1やLDLRAP1によるコンパニオン診断でスタチン製剤の奏効を期待できる症例を選択することができる。今後は奏効を確認した漿液性癌症例と明細胞癌症例を対象に、既発症症例の維持療法もしくは卵巣癌ハイリスク症例の予防薬として用いることや標準治療薬への上乗せを検証する臨床試験の実施が期待される。