| Project/Area Number |
18K06992
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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 49020:Human pathology-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 膵癌 / MAPキナーゼ阻害薬 / 耐性機序 / 耐性機構 / Clusterin / MAPキナーゼ / 阻害薬 / 耐性 |
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| Outline of Final Research Achievements |
It has been shown that an activated MAP kinase contributes to maintain the higher levels of cell growth potential and invasiveness in pancreatic cancer. Therefore, an inhibitor to the MAP kinase is expected to be a promising agent against the pancreatic cancer. However, to date, several clinical trials have failed to demonstrate the efficacy of MAP kinase inhibitor to the patients with pancreatic cancer. In this study, we showed that Clusterin, expressed in pancreatic cancer cells, was involved in the increased cell viability and the resistance to MAP kinase inhibitor. Furthermore, we exhibited the synergistic suppressive effects on cell growth by combination of the treatment with MAP kinase inhibitor and downregulation of Clusterin.
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌は最も予後不良な癌のひとつである。その理由として、顕著な有効性を示す抗がん剤治療法が開発されていないことが挙げられる。したがって膵癌の治療成績を改善するためには、膵癌の発症・進展に関わる分子メカニズムを解明して、その知見に基づく新規治療法の開発が強く望まれる。
本研究では、MAPキナーゼ阻害薬抵抗性獲得に関与する分子Clusterinを同定した。さらに、Clusterinを標的とした治療を併用することでMAPキナーゼ阻害薬の有効性が回復することを示した。今後、ClusterinとMAPキナーゼを標的とする新規膵癌治療法の確立を目指す。
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