2023 Fiscal Year Final Research Report
Targeting epigenetic regulators as a novel combination therapy for gynecologic malignancies harboring SWI/SNF alteration.
| Project/Area Number |
20K18211
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 婦人科悪性腫瘍 / EZH2 / BAZ2A |
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| Outline of Final Research Achievements |
Genomic alterations related to SWI/SNF complex are frequently observed in gynecologic malignencies such as ovarian clear cell carcinoma. It has been reported in several previous researches that EZH2 inhibitors are effective in cancers harboring SWI/SNF-related gene alteration.
In this study, we found that BAZ2A inhibition suppresses proliferation of ovarian cancer cells harboring ARID1A mutation, one of the major SWI/SNF complex genes. Furthermore, we also clarified that a combination therapy with BAZ2A inhibitor and EZH2 inhibitor leads to synergistic anti-tumor effect on ARID1A-mutated ovarian cancer cells.
This study highlighted the potential of BAZ2A as a novel therapeutic target for ARID1A-mutated ovarian cancer in combination with EZH2 inhibition.
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| Free Research Field |
婦人科悪性腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
EZH2阻害剤は臨床応用に向けた臨床研究がおこなわれているが、単独の投与では固形癌において有効な効果を得るには十分でない可能性が指摘されている。卵巣癌細胞を用いてBAZ2A阻害剤を併用することでEZH2阻害剤の効果を増強できる可能性を示したこの研究成果は将来卵巣癌に限らずSWI/SNF複合体関連医遺伝子の異常を有する悪性腫瘍の治療選択を広げる可能性がある。
また、本研究結果はこれまで癌治療領域で注目されることの少なかったBAZ2Aの阻害剤開発の意義を示した点でも重要であると考えられる。
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