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Mutations in the RAS Pathway as Potential Precision Medicine Targets in Treatment of Rhabdomyosarcoma

Research Project

Project/Area Number 17K10123
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Kikuchi Ken  京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (40453104)

Co-Investigator(Kenkyū-buntansha) 柳生 茂希  京都府立医科大学, 医学(系)研究科(研究院), 助教 (10572547)
細井 創  京都府立医科大学, 医学(系)研究科(研究院), 教授 (20238744)
家原 知子  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20285266)
宮地 充  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40584983)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords横紋筋肉腫 / RAF-MEK阻害剤 / RAS変異 / MEK阻害剤 / RAS / プレシジョン医療
Outline of Final Research Achievements

Precision medicine strategies for treating rhabdomyosarcoma (RMS), a childhood malignancy, have not been developed. We examined the effect of selective dual RAF/MEK inhibitor on RMS cell lines. Among the eleven cell lines studied, one NRAS and two HRAS mutated cell lines were detected. RAF/MEK inhibitor inhibited the proliferation and growth in all of the RAS-mutated RMS cell lines, while it induced G1 cell cycle arrest in two of them. G1 cell cycle arrest was accompanied by p21 up-regulation and RB dephosphorylation. RAF/MEK inhibitor also suppressed the in vivo growth of RAS-mutated RMS tumor, and the mice showed improved survival.

Academic Significance and Societal Importance of the Research Achievements

本研究により開発された新しい治療方針・手法は、近年、本申請者らが協力して、インフラ整備と体制確立がなされた本邦の当該小児がんグループスタディの臨床試験において、臨床的にその有効性と安全性を検証し、さらにその結果は本邦の当該がん患児の治療の向上に貢献できると考えている。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Mutations in the RAS pathway as potential precision medicine targets in treatment of rhabdomyosarcoma.2019

    • Author(s)
      Nakagawa N, Kikuchi K, Yagyu S, Miyachi M, Iehara T, Tajiri T, Sakai T, Hosoi H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 512 Issue: 3 Pages: 524-530

    • DOI

      10.1016/j.bbrc.2019.03.038

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Novel allosteric RAF/MEK inhibitor in the treatment of rhabdomyosarooma.2018

    • Author(s)
      Nakagawa N, Kikuchi K, Yagyu S, Iehara T, Sakai T, Hosoi H.
    • Organizer
      第60回日本小児血液・がん学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Mutation of Ras Pathway Should be a Target of Precision Medicine for Rhabdomyosarcoma2017

    • Author(s)
      N. nakagawa, K. Kikuchi, K. Nakamura, T. Tanaka, S. Yagyu, T. Iehara, T. Tajiri, T. Sakai, H. Hosoi
    • Organizer
      49th CONGRESS OF THE INTERNATIONAL SOCIETY OF PAEDIATRIC ONCOLOGY (SIOP)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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