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Basic research for the resistant mechanism and overcoming method in NTRK1 fusion positive cancer

Research Project

Project/Area Number 18K15308
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionKanazawa University

Principal Investigator

Nishiyama Akihiro  金沢大学, がん進展制御研究所, 助教 (80770172)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsNTRK1融合遺伝子 / がん腫横断的 / エヌトレクチニブ / 耐性機序 / NTRK融合遺伝子 / 臓器横断的 / TRK阻害薬 / 高度耐性 / 中等度耐性 / 中枢神経転移
Outline of Final Research Achievements

We focused on NTRK fusion gene which is tumor-agonistic ahead of adaptation of genome oriented therapy in clinical setting. Moreover, overcoming lesions central nervous system (CNS) is considered to be essential and then we produced the brain metastasis model, injecting cancer cells with NTRK fusion gene into mice brain. Inducing resistance of molecular targeted therapy of NTRK1 fusion gene in CNS could lead to the identification of two kinds of resistant mechanism and overcoming method for the resistant was going to be identified. More examinations including animal experiments will be planned from now on.

Academic Significance and Societal Importance of the Research Achievements

実地臨床ではNTRK融合遺伝子に奏効するTRK阻害薬エヌトレクチニブが15例で使用されている。本研究の成果がタイムリーに活用される可能性がある。引き続きこの研究に取り組んでいく。

Report

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

    (3 results)

All 2020 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results)

  • [Journal Article] Foretinib Overcomes Entrectinib Resistance Associated with NTRK1 G667C Mutation in NTRK1 Fusion-Positive Tumor Cells in a Brain Metastasis Model2018

    • Author(s)
      Akihiro Nishiyama
    • Journal Title

      Clinical Cancer Research

      Volume: 24 Issue: 10 Pages: 23572369-23572369

    • DOI

      10.1158/1078-0432.ccr-17-1623

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] NTRK融合遺伝子陽性がんの中枢神経転移における分子標的薬耐性の機構解明と克服薬開発2020

    • Author(s)
      西山明宏
    • Organizer
      第1回日本癌学会若手の会
    • Related Report
      2019 Annual Research Report
  • [Presentation] NTRK1融合遺伝子陽性癌におけるエントレクチニブ耐性機構の解明と耐性克服薬開発2018

    • Author(s)
      西山 明宏
    • Organizer
      第1回金沢大学がん進展制御研究所・国立がんセンター若手研究発表会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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