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Identification of potential compounds that suppress cancer relapse on the drug tolerant colony model(Fostering Joint International Research)

Research Project

Project/Area Number 15KK0317
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionIwate Medical University

Principal Investigator

Nishizuka Satoshi  岩手医科大学, 医歯薬総合研究所, 特任教授 (50453311)

Research Collaborator Liotta Lance  George Mason University, Center for Applied Proteomics and Molecular Medicine, College of Science, University Professor
Mills Gordon  University of Texas, MD Anderson Cancer Center, Department of Systems Biology, Professor and Chair
Kume Kohei  
Ishida Kaoru  
Iwaya Takeshi  
Project Period (FY) 2016 – 2018
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Keywords癌再発 / 薬剤耐性 / 統合解析 / 治療後モニタリング / 腫瘍マーカー / 再発癌 / プロテオミクス解析 / 抗癌剤耐性
Outline of Final Research Achievements

Conventional chemotherapy is performed after gastrectomy with curative intent. However, the relapse rate is still 30-40%. The conventional chemotherapy activates various signaling pathways; therefore it is thought that the inhibition of such pathways would suppress gastric cancer relapse. We identified a compound (a-amanitin) and a molecular targeting drug (GDC-0941), both suppressed gastric cancer relapse. Moreover, we demonstrated that H. pylori infection status was associated with the relapse and circulating tumor DNA predicts the relapse. Finally, we developed an integrated analysis including the levels of genome/transcriptome, protein, cell, model animals, and epidemiology.

Academic Significance and Societal Importance of the Research Achievements

シークエンス技術の発展とともに遺伝子変異を投薬根拠とする「がんゲノム医療」が行政主導のもと推進されている。一方、多くの分子標的薬では標的分画であるタンパクが遺伝子変異によって制御されている証拠は乏しい。本研究は、薬剤耐性の直接的責任分子であるタンパクの動態を基に至適分子標的薬を選定するために立案された。胃癌再発抑制に働く化合物・薬剤は同定されたが、これらが遺伝子変異に起因する証拠は得られなかった。一方、H. pyloriや血中変異DNAの癌診断における意義を確認した。本研究成果は学術的には遺伝子変異による投薬効果の検証を推進し、社会的には遺伝子変異に偏らない癌診断を再認識するという意義がある。

Report

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

    (14 results)

All 2019 2018 2017 2016

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] テキサス大学MDアンダーソン癌センター(米国)2018

    • Year and Date
      2018-01-04
    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] George Mason大学(米国)2016

    • Related Report
      2018 Annual Research Report
  • [Journal Article] A Pipeline for ctDNA Detection Following Primary Tumor Profiling Using a Cancer-Related Gene Sequencing Panel2019

    • Author(s)
      Nishizuka Satoshi S.、Sato Kei A.、Hachiya Tsuyoshi
    • Journal Title

      Methods Mol Biol

      Volume: 1908 Pages: 229-241

    • DOI

      10.1007/978-1-4939-9004-7_16

    • ISBN
      9781493990023, 9781493990047
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver Regeneration Supported by Muse Cells.2018

    • Author(s)
      Nishizuka SS, Suzuki Y, Katagiri H, Takikawa Y.
    • Journal Title

      Adv Exp Med Biol.

      Volume: 1103 Pages: 219-241

    • DOI

      10.1007/978-4-431-56847-6_12

    • ISBN
      9784431568452, 9784431568476
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Helicobacter pylori infection is associated with favorable outcome in advanced gastric cancer patients treated with S-1 adjuvant chemotherapy.2018

    • Author(s)
      Nishizuka SS, Tamura G, Nakatochi M, Fukushima N, Ohmori Y, Sumida C, Iwaya T, Takahashi T, Koeda K; Northern Japan Gastric Cancer Study Consortium.
    • Journal Title

      J Surg Oncol

      Volume: - Issue: 5 Pages: 947-956

    • DOI

      10.1002/jso.24977

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Colony Lysate Arrays for Proteomic Profiling of Drug-Tolerant Persisters of Cancer Cell.2017

    • Author(s)
      Kume K, Nishizuka SS.
    • Journal Title

      Anal Chem

      Volume: 89 Issue: 17 Pages: 8626-8631

    • DOI

      10.1021/acs.analchem.7b01215

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of PI3K mutations and PI3K pathway proteins in advanced gastric cancer2017

    • Author(s)
      Ito C, Nishizuka SS, Ishida K, Uesugi N, Sugai T, Tamura G, Koeda K, Sasaki A
    • Journal Title

      Journal of Surgical Research

      Volume: 212 Pages: 195-204

    • DOI

      10.1016/j.jss.2017.01.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil2017

    • Author(s)
      Ishida K, Ito C, Ohmori Y, Kume K, Sato KA, Koizumi Y, Konta A, Iwaya T, Nukatsuka M, Kobunai T, Takechi T, Nishizuka SS
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 2262-2262

    • DOI

      10.1038/s41598-017-02548-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Genomic and proteomic evaluation in post-therapeutic gastrointestinal cancer relapse2019

    • Author(s)
      Nishizuka SS
    • Organizer
      8th Reverse-Phase Protein Array Global Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Association between Helicobacter pylori infection and outcome in advanced gastric cancer patients treated with S-1 adjuvant chemotherapy2018

    • Author(s)
      Nishizuka SS, Tamura G, Nakatochi M, Iwaya T, Espina VA, Liotta LA, and Koeda K, the Northern Japan Gastric Cancer Consortium
    • Organizer
      American Society of Clinical Oncology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 治療後体内腫瘍量モニタリングツールとしての腫瘍由来循環DNA2018

    • Author(s)
      西塚 哲、岩谷 岳
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Microbiota and Chemotherapy: A Downstream Finding of RPPA Biomarker Screening.2017

    • Author(s)
      Nishizuka S
    • Organizer
      7th Reverse-Phase Protein Array Global Workshop
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] がん診断のためのプローブ/プライマーライブラリー2018

    • Inventor(s)
      西塚 哲、岩谷 岳
    • Industrial Property Rights Holder
      西塚 哲、岩谷 岳
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 胃癌モデル動物の作製方法2017

    • Inventor(s)
      西塚 哲、石田 馨
    • Industrial Property Rights Holder
      西塚 哲、石田 馨
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-080566
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2016-10-04   Modified: 2020-03-30  

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