2023 Fiscal Year Final Research Report
Elucidation of chemoradiation resistance mechanisms for the development of new molecular target drugs for pancreatic cancer
| Project/Area Number |
21H03006
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
Matsuo Yoichi 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40381800)
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| Co-Investigator(Kenkyū-buntansha) |
坪井 謙 名古屋市立大学, 医薬学総合研究院(医学), 講師 (80592500)
今藤 裕之 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (80790641)
林 祐一 名古屋市立大学, 医薬学総合研究院(医学), 助教 (60811726)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | IL-1RI / 膵癌 / 抗癌剤耐性 / 血管新生 / IL-1Ra |
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| Outline of Final Research Achievements |
The prognosis for pancreatic cancer is extremely poor, and recurrence occurs quickly even after radical surgery. Currently, preoperative chemoradiotherapy is recommended, but it is less effective than for other cancers. One reason for this is low sensitivity to treatment. Therefore, elucidating the resistance mechanism and increasing the sensitivity of preoperative treatment will lead to truly curative surgery and will be a breakthrough in improving prognosis. Meanwhile, we succeeded in establishing a pancreatic cancer cell line that is resistant to anticancer drugs and radiation, and as a result of comprehensive genetic analysis, we focused on IL-1RI, a cell membrane receptor for pancreatic cancer. In this study, we revealed that IL-1RI expression increases with resistance, and that it contributes to the tumor progression of pancreatic cancer through NF-κB signaling.
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| Free Research Field |
消化器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
今回着目したIL-1RIの拮抗薬であるIL-1R antagonist（IL-1ra）はすでに欧米で関節リウマチに対して使用されており，膵癌においても臨床応用への実現性が高いと考えている．我々の研究室ではこれまでにIL-1/ IL-1RIシグナルが転写因子NF-κBを活性化し，血管新生因子や接着能や浸潤能を制御していることを世界に先駆けて報告しているが，抗癌剤耐性化によるこれらの機能の変化は未知数である．IL-1/ IL-1RIシグナルを制御することでGem感受性を高め，浸潤や微小転移を術前に今まで以上に制御することができれば，手術の根治性が高まりさらなる予後の改善につながると考える。
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