2018 Fiscal Year Final Research Report
Development of novel therapy for pancreatic cancer targeting Notch/Hes1 signaling
Project/Area Number |
16K09395
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Kobe University (2018) Kyoto University (2016-2017) |
Principal Investigator |
Kodama Yuzo 神戸大学, 医学研究科, 教授 (80378687)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Keywords | 膵癌 / Hes1 |
Outline of Final Research Achievements |
Pancreatic cancer develops from precancerous lesions called ADM and PanIN by accumulation of genetic abnormalities including KRAS gene mutation. In this study, we focused on Notch/Hes1 signaling and aimed to elucidate the pathogenesis of pancreatic cancer and to develop new treatment options. Analysis using human pancreatic cancer specimens and cell lines showed that activation of mutant KRAS gene induced Hes1. Mouse model demonstrated that the formation of pancreatic cancer was almost completely suppressed by knocking out the Hes1 gene. Furthermore, the novel Hes1 inhibitor significantly suppressed the growth of human pancreatic cancer cell lines. These findings suggest that Hes1 plays an essential role in the formation of pancreatic cancer and could be a new therapeutic target.
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Free Research Field |
消化器内科学
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Academic Significance and Societal Importance of the Research Achievements |
膵癌はその5年生存率が10%に満たない難治癌であり、その病態の解明と新規治療開発が急務となっている。膵癌症例の95%はKRAS遺伝子の変異を有し、病態の中心を担っていることが示唆されてきた。本研究では、膵癌に発現が認められるHes1に着目し、その機能解析を行った。その結果、変異KRAS遺伝子の活性化による膵癌の形成には、変異KRASの活性化により誘導されるHes1が必須であることが明らかとなった。また、膵癌細胞にHes1阻害を投与したところ、その増殖が抑制されたことから、Hes1が膵癌の新しい治療標的となる可能性が示唆された。
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