Development of a Novel Therapeutic Approach for Platinum-Resistant Ovarian Cancer by Targeting ATP7B

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16859
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Osaka University
• Principal Investigator: Kakuda Mamoru 大阪大学, 医学部附属病院, 助教 (30923031)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: ATP7B / プラチナ抵抗性卵巣がん / CuSO4

Outline of Final Research Achievements

In platinum-resistant ovarian cancer cell lines with high expression of ATP7B, it was confirmed that knocking down ATP7B expression increases intracellular platinum accumulation and improves platinum sensitivity. Moreover, in clinical specimens, cases exhibiting ATP7B expression were significantly associated with poor prognosis. In vivo model, xenografts of cells with ATP7B knockdown demonstrated significantly enhanced antitumor effects with cisplatin treatment compared to the PBS-treated group, suggesting that ATP7B could be a potential therapeutic target in platinum-resistant ovarian cancer.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

卵巣がんは、予後の悪い疾患の一つとして知られ、手術療法と化学療法による治療法が確立されているが、再発率も高いため治療に難渋する。特に初回治療後半年以内に再発したプラチナ製剤抵抗性の再発症例は予後が非常に悪く、その再発例を対象とした新しい治療法が待たれる。本研究はプラチナ抵抗性の克服が急務であるプラチナ抵抗性卵巣がんにおいてATP7Bが治療ターゲットとなりうることを示した。