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Development of reverse-phase protein array platform for analyzing tissue samples and identification of biomarkers to guide the use of a TNIK inhibitor

Research Project

Project/Area Number 16K14627
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor diagnostics
Research InstitutionNational Cancer Center Japan

Principal Investigator

Masuda Mari  国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (70435717)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords精密医療 / 逆相タンパクアレイ / RPPA / リン酸化タンパク / シグナル経路 / バイオマーカー / 大腸がん / Wnt シグナル / シグナルプロファイル / 分子標的治療薬 / 高精度医療 / Wntシグナル / トランスレーショナルリサーチ / 細胞・組織 / リン酸化プロファイリング / プロテオーム / TNIK阻害剤 / 癌
Outline of Final Research Achievements

Despite the early successes of targeted therapies and improvements in sequencing technology over the last two decades, genomics-driven precision oncology has helped only a minority of cancer patients. It has become apparent that genomic profiling in itself is limited with respect to optimal selection of patients for targeted therapy. Proteomics-, but not genomics-, based approaches capture biological processes that directly contribute to cancer pathogenesis. Reverse-phase protein array (RPPA) is well suited for investigating the signaling status in a limited amount of clinical samples. We have previously developed RPPA platform for analyzing cells. In this research project, we established a RPPA platform for analyzing tumor specimens. In addition, we have optimized the method of signal detection suited to RPPA analysis for tissue samples. Using this platform, we identified a potential biomarker for monitoring the effect of a TNIK inhibitor which we previously developed.

Academic Significance and Societal Importance of the Research Achievements

がん精密医療はゲノム医療が中心であるが、検査後に治療が可能な症例は限られており、更なる改善が望まれている。腫瘍内のシグナル経路の異常をごく微量のサンプルから正確に把握できる逆相タンパクアレイを精密医療に応用できれば、現在、治療選択肢の無い患者にも薬剤の提示ができる可能性がある。本研究によって、組織RPPA基盤の確立することができれば、精密医療の質の向上をもたらす可能性がある。また、本基盤を用いてTNIK阻害剤のコンパニオンマーカー候補が同定できれば、薬剤開発を促進し、新たな大腸がん治療薬の創出に役立つと考えられるため社会への貢献度は高く重要な意義がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (42 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (25 results) (of which Int'l Joint Research: 18 results,  Invited: 7 results) Book (2 results) Remarks (8 results)

  • [Int'l Joint Research] George Mason University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] George Mason University(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Hunting hidden pieces of signaling pathways in hepatocellular carcinoma.2019

    • Author(s)
      Masuda M.
    • Journal Title

      HepatoBiliary Surg Nutr.

      Volume: 1 Issue: 1 Pages: 74-76

    • DOI

      10.21037/hbsn.2018.10.10

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Signaling pathway profiling using reverse-phase protein array and its clinical applications2017

    • Author(s)
      Masuda Mari、Yamada Tesshi
    • Journal Title

      Expert Review of Proteomics

      Volume: 14 Issue: 7 Pages: 607-615

    • DOI

      10.1080/14789450.2017.1344101

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The emergence of TNIK as a therapeutic target for colorectal cancer.2017

    • Author(s)
      Masuda M, Yamada T.
    • Journal Title

      Expert Opin Ther Targets.

      Volume: 4 Issue: 4 Pages: 353-355

    • DOI

      10.1080/14728222.2017.1297799

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The emergence of TNIK inhibitors in cancer therapeutics.2017

    • Author(s)
      Yamada T, Masuda M.
    • Journal Title

      Cancer Sci.

      Volume: 印刷中 Issue: 5 Pages: 818-823

    • DOI

      10.1111/cas.13203

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TNIK inhibition abrogates colorectal cancer stemness2016

    • Author(s)
      Masuda M, Uno Y, Ohbayashi N, Ohata H, Mimata A, Kukimoto-Niino M, Moriyama H, Kashimoto S, Inoue T, Goto N, Okamoto K, Shirouzu M, Sawa M, Yamada T.
    • Journal Title

      Nature Comm.

      Volume: 7 Issue: 1 Pages: 12586-12586

    • DOI

      10.1038/ncomms12586

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Traf2-and Nck-interacting kinase (TNIK) inhibitor, NCB-0846, suppresses TGF-β1-induced epithelial-mesenchymal transition in lung cancer.2018

    • Author(s)
      T. Sugano, M. Masuda, Y. Uno, N. Goto, M. Seike, M. Sawa, A. Gemma, T. Yamada.
    • Organizer
      AACR Annual meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TRAF2 and NCK-interacting protein kinase (TNIK) regulates cancer stemness and adipogenesis of osteosarcoma cells.2018

    • Author(s)
      T. Hirozane, M. Masuda, N. Goto, T. Sugano, N. Asano, E. Kobayashi, K. Horiuchi, H. Morioka, A. Kawai, M. Sawa, M. Matsumoto, M. Nakamura, T. Yamada.
    • Organizer
      AACR Annual meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肉腫のプロテオゲノミクス解析:国際がんプロテオゲノミクスコンソーシアム(ICPC).2018

    • Author(s)
      近藤格、服部恵美、塩澤久美子、尾野雅哉、増田万里、山田哲司.
    • Organizer
      日本質量分析学会・日本プロテオーム学会2018年合同大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肉腫のプロテオゲノミクス解析:国際がんプロテオゲノミクスコンソーシアム(ICPC).2018

    • Author(s)
      近藤格、服部恵美、尾野雅哉、増田万里、川井章、山田哲司.
    • Organizer
      第14 日本臨床プロテオゲノミクス研究会.
    • Related Report
      2018 Annual Research Report
  • [Presentation] TNIK is a novel molecular target for osteosarcoma treatment and controls osteosarcoma cell fate.2018

    • Author(s)
      Toru Hirozane, Mari Masuda, Naoko Goto, Teppei Sugano, Naofumi Asano, Eisuke Kobayashi, Akira Kawai, Keisuke Horiuchi, Morio Matsumoto, Masaya Nakamura, Masaaki Sawa, Hideo Morioka, Tesshi Yamada.
    • Organizer
      2018 CTOS Annual Meeting,
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clarification of the Signaling Network Affected by the TNIK Inhibitor, NCB-0846, Using Reverse-phase Protein Array.2018

    • Author(s)
      Mari Masuda, Takeomi Inoue, Yuko Uno, Naoko Goto, Masaaki Sawa and Tesshi Yamada.
    • Organizer
      The Human Proteome Organization (HUPO) 2018 meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 網羅的ゲノム解析を用いた肺カルチノイドの新規治療標的遺伝子の同定.2018

    • Author(s)
      宮永晃彦、増田万里、蔦幸治、西島伸彦、清家正博、浅村尚生、弦間昭彦、山田哲司.
    • Organizer
      第59回日本肺癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸がん幹細胞の遺伝子転写を標的とした新規分子標的治療薬の開発.2018

    • Author(s)
      増田万里、弘實透、宇野佑子、澤匡明、山田哲司.
    • Organizer
      第14回日本がん分子標的治療学会・TRワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] Application of the TNIK inhibitor, NCB-0846, to colorectal cancer treatment and beyond.2018

    • Author(s)
      Masuda M
    • Organizer
      8th Global Reverse Phase Protein Array Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん精密医療における逆相タンパク基盤の有用性2018

    • Author(s)
      増田万里
    • Organizer
      第15回北里疾患プロテオーム研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] がん高精度医療における逆相タンパクアレイ基盤の有用性2018

    • Author(s)
      増田万里
    • Organizer
      北里疾患プロテオーム研究会 増田
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Application of Proteomic Technology in Development of Novel TNIK Inhibitor Blocking Wnt Signaling2017

    • Author(s)
      Mari Masuda, Yuko Uno, Shigeki Kashimoto, Hideki Moriyama, Masaaki Sawa and Tesshi Yamada
    • Organizer
      日本プロテオーム学会2017年大会JHUPO第15回大会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Preclinical development of NCB-0846, a novel TNIK inhibitor that blocks Wnt signaling in colorectal cancer2017

    • Author(s)
      Mari Masuda, Takeomi Inoue, Yuko Uno, Hideki Moriyama, Shigeki Kashimoto, Naoko Goto, Masaki Sawa and Tesshi Yamada
    • Organizer
      第76回日本癌学会月術総会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規TNIK 阻害薬によるEMT 制御2017

    • Author(s)
      菅野哲平、増田万里、宇野佑子、森山英樹、後藤尚子、清家正博、澤匡明、弦間昭彦、山田哲司
    • Organizer
      第76回日本癌学会月術総会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] TNIK は骨肉腫の新規治療標的となりうる2017

    • Author(s)
      弘實透、増田万里、後藤尚子、浅野尚文、小林英介、川井章、堀内圭輔、澤匡明、山田哲司
    • Organizer
      第76回日本癌学会月術総会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] TNIK 阻害剤はWnt シグナルを減弱させてがん幹細胞画分を減少させる2017

    • Author(s)
      宇野佑子、増田万里、森山英樹、澤匡明、山田哲司
    • Organizer
      第76回日本癌学会月術総会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 弘實透,増田万里,浅野尚文,小林英介,川井章,堀内圭輔,松本守雄,澤匡明,森岡秀夫,中村雅也,山田哲司2017

    • Author(s)
      TRAF2 and NCK-interacting protein kinase(TNIK)は骨肉腫の分子標的となりうる
    • Organizer
      日本整形外科学会基礎学術集会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 弘實 透,増田万里,後藤尚子,菅野哲平,浅野尚文,小林英介,川井 章,堀内圭輔,松本守雄,中村雅也,澤 匡明,森岡秀夫,山田哲司2017

    • Author(s)
      骨肉腫治療におけるTNIK阻害剤の可能性
    • Organizer
      分子腫瘍マーカー研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] A novel TNIK inhibitor potently downregulates cancer stem cell population through attenuation of Wnt signaling2017

    • Author(s)
      Yuko Uno, Hideki Moriyama, Shigeki Kashimoto, Mari Masuda, Masaaki Sawa, Tesshi Yamada
    • Organizer
      AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Elucidation of Signaling Pathways Affected by TNIK Inhibitor, NCB-0846, Using Reverse-Phase Protein Array2017

    • Author(s)
      Mari Masuda, Takeomi Inoue, Yuko Uno, Masaaki Sawa and Tesshi Yamada
    • Organizer
      RPPA Global Workshop 2017 Dublin
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Therapeutic target discovery by cancer proteomics in the era of large-scale genome-resequencing2017

    • Author(s)
      Tesshi Yamada and Mari Masuda
    • Organizer
      HUPO 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Developing therapeutic intervention of Wnt signaling pathway in colorectal cancer2016

    • Author(s)
      Mari Masuda, Yuko Uno, Hirokazu Ohata, Hideki Moriyama, Naoko Goto, Koji Okamoto, Masaki Sawa and Tesshi Yamada
    • Organizer
      The 76the Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel Traf2- and Nck-interacting kinase inhibitor suppresses epithelial mesenchymal transition2016

    • Author(s)
      Teppei Sugano, Mari Masuda, Yuko Uno, Hideki Moriyama, Naoko Goto, Masahiro Seike, Masaaki Sawa, Akihiko Gemma, Tesshi Yamada
    • Organizer
      The 76the Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Yuko Uno, Mari Masuda, Hideki Moriyama, Masaaki Sawa, Tesshi Yamada2016

    • Author(s)
      Inhibition of TNIK impairs cancer cell motility through attenuation of Wnt signaling
    • Organizer
      The 76the Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preclinical Characterization Of A Novel TNIK Inhibitor, NCB-0846, By Proteomic Profiling Of Signaling Pathways Using Reverse-Phase Protein Array2016

    • Author(s)
      Mari Masuda, Takeomi Inoue, Yuko Uno, Masaaki Sawa and Tesshi Yamada
    • Organizer
      6th Global Reverse Phase Protein Array Workshop
    • Place of Presentation
      NMI Naural and Medical Science Institute at the University of Tubingen, Germany
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Biomarkers in Cancer Therapy2019

    • Author(s)
      Akihiko Miyanaga, Mari Masuda, Tesshi Yamada
    • Total Pages
      5
    • Publisher
      Springer Nature
    • Related Report
      2018 Annual Research Report
  • [Book] 大腸がんの幹細胞増殖を抑える新規化合物発見から創薬へ2017

    • Author(s)
      増田万里
    • Total Pages
      1
    • Publisher
      日経サイエンス
    • Related Report
      2017 Research-status Report
  • [Remarks] 個別医療に有用なバイオマーカーの開発

    • URL

      https://www.ncc.go.jp/jp/ri/division/genetics/project/030/index.html#kobetsu

    • Related Report
      2018 Annual Research Report
  • [Remarks] 個別医療に有用なバイオマーカーの開発

    • URL

      https://www.ncc.go.jp/jp/ri/department/clinical_proteomics/project/030/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 国立がん研究センター研究所・連携研究室(増田グループ)

    • URL

      https://www.ncc.go.jp/jp/ri/division/genetics/project/index.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 大腸がん幹細胞を抑制する新規化合物を創出

    • URL

      http://www.ncc.go.jp/jp/information/pr_release/press_release_20160826.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 大腸がん幹細胞を抑制する新規化合物を創出

    • URL

      http://www.amed.go.jp/news/release_20160826.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 大腸がん幹細胞を抑制する新規化合物NCB-0846を同定-国がんら

    • URL

      http://www.qlifepro.com/news/20160830/identifying-novel-compounds-which-inhibit-ncb-0846-colon-cancer-stem-cells.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 大腸がん幹細胞を抑制、がん細胞を根絶できる化合物 がん研、理研などが実用化目指す

    • URL

      http://www.agingstyle.com/2016/09/11001414.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 【最新医療】大腸がんの幹細胞の働きを抑える新規治療薬開発に期待

    • URL

      http://www.akiramenai-gan.com/medical_contents/disease/disease03/61931/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-06-09  

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