Identification of potential compounds that suppress cancer relapse on the drug tolerant colony model(Fostering Joint International Research)
| Project/Area Number |
15KK0317
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| 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
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| Project Period (FY) |
2016 – 2018
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(14 results)
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[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
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Journal Title
Sci Rep.
Volume: 7
Issue: 1
Pages: 2262-2262
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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