Identification of sentization markers and elucidation of drug resistance mechanism for FGFR inhibitors on cholangiocarcinoma
| Project/Area Number |
16K09400
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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 |
Gastroenterology
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| Research Institution | Nagoya City University |
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Principal Investigator |
Miyabe Katsuyuki 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00543985)
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| Co-Investigator(Kenkyū-buntansha) |
林 香月 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (00405200)
内藤 格 名古屋市立大学, 医薬学総合研究院(医学), 講師 (30527750)
吉田 道弘 名古屋市立大学, 医薬学総合研究院(医学), 助教 (20636328)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | FGFR阻害剤 / 胆管癌 / 薬剤耐性 / 薬剤抵抗性 / FGFR / 胆道癌 |
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| Outline of Final Research Achievements |
We investigated drug resistance mechanism for Fiber Growth Factor Receptor (FGFR) inhibitors on cholangiocarcinoma.
In an in-vitro study, we generated a cell line which possessed drug resistance against FGFR inhibitors using a KMCH cell stain harboring the fibroblast growth factor receptor (FGFR) amplifications. Additionally, we are analyzing what mechanisms are associated with drug resistance for FGFR inhibitors using the cell line.
In an in-vivo study, Copy Number Variation (CNV) analysis was performed using patients-derived xenografts (PDX) administered FGFR inhibitors (Ponatinib or BGJ398) and possessed drug resistance against the inhibitors. Compared with control PDXs, the drug-resistance PDX had some specific gene aberrations. Furthermore, a total of 22 gene aberrations were detected by the comparison between the PDX and a real human tissue sample administered Ponatinib. We are further investigating the role of detected genes by exome sequence using the PDX samples.
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| Academic Significance and Societal Importance of the Research Achievements |
FGFR 阻害剤の薬剤抵抗性獲得に寄与する機序をを検討した。すでにFGFR阻害剤を投与されたサンプルおよび投与されていないサンプルとの比較をすることにより、薬剤耐性に関わる遺伝子を探り出すことができた。FGFR阻害剤は近年胆管癌の治療に有望な分子標的薬として注目されており、一部の胆管癌患者の予後を延長するものと期待されている。その薬剤耐性機序を探るうえでのヒントを見つけ出すことにより、本阻害剤が実際の患者に投与され、耐性となった際の次の治療戦略を考える上で、本研究が重要な意義を果たすものと思われる。
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Report
(5 results)
Research Products
(8 results)
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[Journal Article] Laterally Spreading Adenocarcinoma Involving the Lower Bile Duct and Duodenum Expressing Heterogeneous Immunohistochemical Phenotypes2019
Author(s)
Miyabe K, Notohara K, Asano G, Kachi K, Kato A, Natsume M, Jinno N, Hori Y, Yoshida M, Naitoh I, Hayashi K, Ohara H, Takahashi S, Kataoka H.
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Journal Title
Internal Medicine
Volume: 58
Issue: 21
Pages: 3087-3092
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2019-11-01
Related Report
Peer Reviewed / Open Access
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