2021 Fiscal Year Final Research Report
Development of tumor-host integrative therapies to overcome the refractory nature of uterine serous carcinoma
| Project/Area Number |
18K09287
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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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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
B Tsukasa 岩手医科大学, 医学部, 教授 (60508240)
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| Co-Investigator(Kenkyū-buntansha) |
村上 隆介 京都大学, 医学研究科, 特定病院助教 (40782363)
万代 昌紀 京都大学, 医学研究科, 教授 (80283597)
Brown John 京都大学, 医学研究科, 講師 (90583188)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | 子宮体癌 / 漿液性癌 / 治療抵抗性 / 動物モデル |
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| Outline of Final Research Achievements |
Serous uterine carcinoma (SEC), which accounts for 10% of all uterine cancers, is highly metastatic and often resistant to treatment. In this study, through comprehensive genetic analysis of SEC, we found that Myc activity regulates the malignant nature of SEC and its downstream factors may be potential therapeutic targets. Furthermore, since the anti-tumor immune evasion mechanism was enhanced in SEC in human clinical specimens, we also focused on the anti-tumor immune evasion mechanism and created a mouse model of SEC under normo-immune conditions. Using this model, we searched for anti-tumor immune evasion mechanisms between cancer and host, and found that CCL7 secretion from tumor cells was an important factor as a transduction signal. We submitted these results as an original research article and have begun to expand on our previous findings and search for therapies that act on cancer-host signaling.
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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 |
現在までに有効な治療法の無いSECについてはドライバー遺伝子や治療候補薬剤を同定したという報告もあるが、再現性を示す報告や免疫健常生体内での有効性を示す報告は見られない。我々はこれまで国内外の研究者の協力を得て多コホート・多細胞株での検討を重ねmyc/STAT1がSECの多様な治療抵抗性を司り、予後不良因子となることを明らかにしてきた。これまでの課題を基にSECの免疫健常マウスモデルを作成し、対照モデルとの比較でSECの抗腫瘍免疫逃避機構の一端を明らかにした。この成果は今後のSEC研究への発展に留まらず、女性の健康を蝕む他癌腫にも応用できる可能性が高く、本研究の学術的独自性は高いと考えられる。
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