2018 Fiscal Year Final Research Report
The KANK1 pathway may be a novel therapeutic target for ovarian clear cell carcinoma
| Project/Area Number |
16K11151
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小見 英夫 岩手医科大学, 医学部, 助教 (20382608)
利部 正裕 岩手医科大学, 医学部, 特任講師 (30382609)
佐藤 誠也 岩手医科大学, 医学部, 助教 (30621007)
杉山 徹 岩手医科大学, 医学部, 教授 (40162903)
竹内 聡 岩手医科大学, 医学部, 特任准教授 (60252772)
小島 淳美 岩手医科大学, 医学部, 講師 (60508753)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 卵巣明細胞癌 / Aurora kinase A / バイオマーカー / シスプラチン |
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| Outline of Final Research Achievements |
We examined the incidence of Aurora kinase A (Aurora-A) protein expression in ovarian clear cell carcinoma (OCCC) tumor tissues and its correlation with clinical parameters. In addition, we assessed the efficacy of ENMD-2076, an Aurora-A inhibitor, in combination with chemotherapeutic agents for the treatment of OCCC.
The expressions of Aurora-A protein were found in 96% of OCCC. Increased Aurora-A expression was associated with significantly worse overall survival of FIGO stages IC3 to IV patients (21% vs 77%). Multivariate analysis revealed that Aurora-A expression was an independent prognostic factor for stages IC3 to IV OCCC patients. Furthermore, synergistic effects were observed with ENMD-2076 in combination with cisplatin or SN-38 in 4 of the 6 tested cell lines. ENMD-2076 dramatically enhanced apoptosis and cell cycle arrest at the G2/M phase induced by cisplatin.
Aurora-A is a promising biomarker that is predictive of patient outcomes and a potential target for OCCC.
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| Free Research Field |
婦人科腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
卵巣明細胞癌において、腫瘍組織中のAurora-A蛋白発現強度は有望な予後予測マ－カ－であることが示唆された。また、基礎的検討においてAurora-A阻害剤とシスプラチンとの併用療法の有効性が示唆された。
したがって、難治性卵巣癌の一つである明細胞癌において、Aurora-Aは重要なバイオマーカーであり、Aurora-A阻害剤は明細胞癌患者の予後を改善する可能性が示された。
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