Development of new treatment targeting BRAF V600E mutation in malignant glioma
| Project/Area Number |
16K10762
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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 |
Neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
Kuroda Jun-Ichiro 熊本大学, 大学院生命科学研究部(医), 助教 (90536731)
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| Co-Investigator(Kenkyū-buntansha) |
中村 英夫 久留米大学, 医学部, 准教授 (30359963)
篠島 直樹 熊本大学, 病院, 講師 (50648269)
牧野 敬史 熊本大学, 病院, 非常勤診療医師 (90381011)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 悪性神経膠腫 / BRAFV600E変異 / BRAF阻害薬 / BRAFv600e変異 / brain tumor / gliobalstoma / BRAF V600E / vemurafenib / BRAFv600e / molecular targetting / epithelioid glioblastoma |
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| Outline of Final Research Achievements |
BRAF V600E mutation causes activation of the RAS-MAP kinase pathway has also been recently reported in malignant glioma. Some malignant gliomas with this mutation have a poor prognosis due to cerebrospinal fluid dissemination and metastasis to other organs even after standard treatment consisting of removal, radiation therapy and chemotherapy. The purpose of this study is to establish the BRAF V600E mutant glioblastoma cell line, clarify the efficacy and pharmacology of BRAF inhibitors in preclinical studies, and future clinical development. We succeeded in establishing one cell line from glioblastoma with BRAF V600E mutation, but in vivo experiments did not lead to the establishment of orthotopic transplantation model and metastasis model of the cell line.We obtained new findings by analyzing clinical specimens.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性脳腫瘍は脳の臓器特異性から手術や薬剤を使用した治療法に制限を受け、予後も不良である。一方で脳腫瘍研究の進歩から治療ターゲットとなりうる遺伝子変異も多数、報告されてきている。本研究ではBRAFV600E 変異に注目して、悪性脳腫瘍の臨床例から本変異を有する細胞株を樹立した。この成果によってBRAF阻害薬の薬効検討や耐性獲得機序の解明の研究に資するという学術的意義を持つ、また、研究成果から悪性脳腫瘍に有効な新規治療法開発につながるという社会的意義を有する。
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Report
(5 results)
Research Products
(4 results)
