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Screening of novel markers for drug sensitivity in clear cell renal cell carcinoma with deep kinome profiling

Research Project

Project/Area Number 17K15014
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor diagnostics
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

Abe Yuichi  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 プロテオームリサーチプロジェクト, 協力研究員 (30731632)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsリン酸化プロテオミクス / キノーム / 薬剤感受性 / 淡明型腎細胞癌 / 淡明型腎細胞がん / キナーゼ活性測定 / キナーゼ阻害剤 / リン酸化プロテオーム / 分子標的 / がん耐性 / チロシンキナーゼ
Outline of Final Research Achievements

We performed primary culture from surgical tissues of clear cell renal cell carcinoma (ccRCC), and succeeded in cloning 25 cell lines. 11 clones out of the 25 cell lines were subjected to measurement of drug sensitivity asssay to Sunitinib, Axitinib, Everolimus, and Cabozantinib. We obserbed various patterns of drug sensitivity between each cell clone.
We conducted proteomic and phosphoproteomic analysis of the 10 clones of ccRCC primary cell lines. We identified 6,486 proteins and 33,652 phosphosites (including 21,407 class-1 sites) from the primary cell lines.
We further plan to integrate the proteomic and phosphoproteomic data, and calculate kinome activity profiling. Comparison of the kinome profiling will reveals modulated phosphosignalings that are speciific to resistant groups, and lead us novel candidates as markers for drug sensitivity. We further plan to perform functional analysis of those candidates in cell lines by using siRNA or CRISPR/Cas9 system.

Academic Significance and Societal Importance of the Research Achievements

腎細胞癌は癌全体の3~5%を占めており、その発生率は毎年2%ずつ増加している。そのため、効率的な淡明腎細胞癌への治療戦略の構築は公衆衛生学的に大きな意義がある。本研究により患者の臨床情報と淡明腎細胞癌キノーム特性との関連に対する理解が深まり、より効率的なマルチキナーゼ標的薬による治療法の構築が期待される。またキノームは他の癌腫でも重要な治療標的として認識されているため、本研究で構築する高深度キノーム解析系は他の癌腫にも応用できる。すなわち本研究計画を遂行する事でキナーゼを標的としたプレシジョンメディスン(精密医療)の成立に繋がり、国民医療費の大幅な低減に貢献できる意義がある。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report

Research Products

(6 results)

All 2018 2017

All Journal Article Presentation Patent(Industrial Property Rights)

  • [Journal Article] Improved phosphoproteomic analysis for phosphosignaling and active-kinome profiling in Matrigel-embedded spheroids and patient-derived organoids2018

    • Author(s)
      Abe Yuichi、Tada Asa、Isoyama Junko、Nagayama Satoshi、Yao Ryoji、Adachi Jun、Tomonaga Takeshi
    • Journal Title

      Scientific Reports

      Volume: 8 Pages: 11401-11401

    • DOI

      10.1038/s41598-018-29837-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deep Phospho- and Phosphotyrosine Proteomics Identified Active Kinases and Phosphorylation Networks in Colorectal Cancer Cell Lines Resistant to Cetuximab.2017

    • Author(s)
      Abe Y, Nagano M, Kuga T, Tada A, Isoyama J, Adachi J, Tomonaga T.
    • Journal Title

      Scientific Reports

      Volume: 7(1) Pages: 10463-10463

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 網羅的チロシンリン酸化プロテオミクス解析法の構築2018

    • Author(s)
      阿部雄一、多田亜沙、磯山純子、長野麻衣子、久家貴寿、佐藤彩子、足立淳、朝長毅
    • Organizer
      MSP2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Deep Phospho- and Phosphotyrosine Proteomics Identified Active Kinases and Phosphorylation Networks in Colorectal Cancer Cell Lines Resistant to Cetuximab2017

    • Author(s)
      Yuichi Abe, Maiko Nagano, Asa Tada, Jun Adachi, Takeshi Tomonaga
    • Organizer
      The 16th Human proteome Organization World Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 治療標的である活性化キナーゼのスクリーニング方法2018

    • Inventor(s)
      朝長毅、阿部雄一
    • Industrial Property Rights Holder
      朝長毅、阿部雄一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-037894
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 治療標的である活性化キナーゼのスクリーニング方法2018

    • Inventor(s)
      国立研究開発法人医薬基盤健康栄養研究所
    • Industrial Property Rights Holder
      国立研究開発法人医薬基盤健康栄養研究所
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-037894
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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