Novel therapeutic strategy targeting EpCAM-positive ovarian cancer stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K20151
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kumamoto University
• Principal Investigator: Motohara Takeshi 熊本大学, 大学院生命科学研究部(医), 講師 (10457591)
• Research Collaborator: Katabuchi Hidetaka
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 卵巣癌 / 癌幹細胞 / 抗癌剤治療抵抗性 / EpCAM

Outline of Final Research Achievements

Epithelial ovarian cancer is a highly lethal malignancy and overcoming chemoresistance is the major challenging in treating ovarian cancer patients. Even though ovarian cancer stem cells have not been completely elucidated, these cells are believed to play crucial roles in chemoresistance and relapse of ovarian cancer. Previous studies have supported the premise that EpCAM is one of the cell surface markers associated with cancer stem cells in many solid cancers, including ovarian cancer.
In this study, we demonstrated the functional role of EpCAM in the resistance to platinum-based chemotherapy. We also found that EpCAM-targeted therapies using adecatumumab showed a significant inhibition of ovarian cancer cell proliferation and tumor growth in in vitro assays and in vivo mouse models.
EpCAM expression may represent a promising therapeutic target to effectively extirpate the cancer stem cells as the root of ovarian cancer.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

今回の研究では、卵巣癌におけるEpCAMの分子生物学的な役割として、特に抗癌剤治療抵抗性に密接に関わっていることを明らかにした。さらにわれわれは、EpCAM陽性の腫瘍細胞に対する新規分子標的薬が、EpCAM陽性の卵巣癌細胞に対する著明な抗腫瘍効果を有することを実験的に証明した。これらの結果は、EpCAMを標的とした有望な分子標的薬というツールを通じて、卵巣癌幹細胞を標的とした新たな治療戦略の開発に繋がっていくことが期待される。