2018 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number	15KK0317
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research)
Allocation Type	Multi-year Fund
Research Field	Digestive surgery
Research Institution	Iwate 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
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
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.
Free Research Field	システム医学
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。