Personalized therapy for pancreatic cancer focused on FGFR-4, a novel molecular target
| Project/Area Number |
16K10613
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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 |
Digestive surgery
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Ishiwata Toshiyuki 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (90203041)
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| Co-Investigator(Kenkyū-buntansha) |
吉村 久志 日本獣医生命科学大学, 獣医学部, 講師 (70645241)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 膵癌 / 分子標的治療 / FGFR-4 / 個別化治療 / SNP / FGFR-4阻害剤 / 高齢者がん |
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| Outline of Final Research Achievements |
In the present study, we examined the expression and the roles of fibroblast
growth factor receptor-4 (FGFR-4) and its SNP in human pancreatic cancer, which is increasing in frequency among the elderly. FGFR-4 expression was immunohistochemically detected in approximately 50% of pancreatic ductal adenocarcinomas. FGFR-4 expression correlated positively with larger primary tumors and more advanced stages of pancreatic cancer. Expression levels of FGFR-4 in 6 human pancreatic cancer cell lines were different from levels of both IIIb and IIIc isoforms of FGFR-1, 2, and 3. The G388R SNP was detected in half of the pancreatic cancer cell lines examined. An inhibitor of FGFR-4 inhibited signal transduction in pancreatic cancer cells, and reduced cell growth. These findings suggest that FGFR-4 is a novel therapeutic target for some types of pancreatic cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢者に増加する膵癌は極めて予後不良な難治性癌で、癌細胞の表面には様々な増殖因子受容体が過剰発現している。線維芽細胞増殖因子受容体のFGFR-4が、乳癌、卵巣癌、膵癌などで過剰に発現していることが明らかになり、一部の癌では、FGFR-4のG388RのSNPが予後の増悪と関連しているとの報告もみられている。膵癌におけるFGFR-4の発現とSNPの存在、さらにその役割について研究を行なった。FGFR-4阻害剤を投与することで、膵癌培養細胞の細胞内シグナル伝達が抑制され、癌の細胞増殖が抑えられた。今回の研究から、FGFR-4の抑制がヒト膵癌の新たな治療標的となる可能性が示された。
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Report
(4 results)
Research Products
(6 results)
