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Elucidation of drug-resistance induction mechanism and construction of the new therapy targeting epigenome change

Research Project

Project/Area Number 17K10696
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionOsaka University

Principal Investigator

Eguchi Hidetoshi  大阪大学, 医学系研究科, 教授 (90542118)

Co-Investigator(Kenkyū-buntansha) 和田 浩志  地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 消化器外科 副部長 (00572554)
後藤 邦仁  大阪大学, 医学系研究科, 助教 (10362716)
山田 大作  地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 消化器外科医長 (60571396)
岩上 佳史  大阪大学, 医学系研究科, 助教 (60597441)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords抗癌剤耐性 / 放射線耐性 / 癌幹細胞 / c-Met / エピゲノム / 上皮間葉転換 / ドラッグ・リポジショニング
Outline of Final Research Achievements

In the treatment of pancreatic cancer and biliary tract cancer, chemotherapy or radiotherapy is frequently used; however, it has been reported that such therapies may induce alteration of cancer cell’s characters, leading to treatment resistance. In this study, the mechanisms of treatment resistance that is acquired through chemotherapy or radiotherapy was investigated. This study demonstrated that one of the important markers for pancreatic cancer stem cells, c-Met, was induced by irradiation, and that the induction of c-Met increased the malignancy (invasion and migration) of cancer cells. It was also shown that c-Met inhibitors could suppress the increase in malignancy.

Academic Significance and Societal Importance of the Research Achievements

予後の不良な膵癌や胆道癌では、手術治療だけでは根治は難しく、今後も放射線治療や抗癌剤治療は頻用されると推察される。しかしそのような治療法が根治の妨げとなる可能性があることを本研究で証明した。さらに本研究では、そのような抗癌治療の際に癌幹細胞の誘導を抑制する「癌幹細胞誘導抑制併用化学療法」の概念を樹立した。この併用療法を臨床応用することにより、癌患者の予後改善、特に根治率の向上が期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Endogenous CXCL9 affects prognosis by regulating tumor-infiltrating NK cells in intrahepatic cholangiocarcinoma2020

    • Author(s)
      Fukuda Y, Asaoka T, Eguchi H, Yokota Y, Kubo M1, Kinoshita M, Urakawa S, Iwagami Y, Tomimaru Y, Akita H, Noda T, Gotoh K, Kobayashi S, Hirata M, Wada H, Mori M, Doki Y.
    • Journal Title

      Cancer Sci.

      Volume: 111 Issue: 2 Pages: 323-333

    • DOI

      10.1111/cas.14267

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma2019

    • Author(s)
      Kubo Masahiko、Gotoh Kunihito、Eguchi Hidetoshi、Kobayashi Shogo、Iwagami Yoshifumi、Tomimaru Yoshito、Akita Hirofumi、Asaoka Tadafumi、Noda Takehiro、Takeda Yutaka、Tanemura Masahiro、Mori Masaki、Doki Yuichiro
    • Journal Title

      Annals of Surgical Oncology

      Volume: 27 Issue: 2 Pages: 610-619

    • DOI

      10.1245/s10434-019-07927-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Hydrogen Peroxide Activatable Gemcitabine Prodrug for the Selective Treatment of Pancreatic Ductal Adenocarcinoma2019

    • Author(s)
      Matsushita Katsunori、Konno Masamitsu、Eguchi Hidetoshi、Koseki Jun、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi、Obika Satoshi
    • Journal Title

      ChemMedChem

      Volume: 14 Issue: 15 Pages: 1384-1391

    • DOI

      10.1002/cmdc.201900324

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 膵癌の術前療法は化学療法をすべきか化学放射線療法をすべきか2018

    • Author(s)
      江口 英利, 森 正樹, 土岐 祐一郎
    • Journal Title

      癌の臨床

      Volume: 63 Pages: 413-417

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fatty Acid-Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer.2017

    • Author(s)
      Hata T, Kawamoto K, Eguchi H, Kamada Y, Takamatsu S, Maekawa T, Nagaoka S, Yamada D, Iwagami Y, Asaoka T, Noda T, Wada H, Gotoh K, Masamune A, Miyoshi E, Mori M, Doki Y.
    • Journal Title

      Pancreas

      Volume: 46 Issue: 10 Pages: 1259-1266

    • DOI

      10.1097/mpa.0000000000000943

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵癌術前化学放射線療法によりc-Met発現を助長するmicroRNAの検討2018

    • Author(s)
      森 総一郎
    • Organizer
      第77回日本癌学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Borderline resectable膵癌に対する化学療法と化学放射線療法に関する考察2017

    • Author(s)
      江口 英利, 森 正樹, 土岐 祐一郎
    • Organizer
      日本消化器外科学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脈管浸潤陽性膵癌の術前療法は化学療法をすべきか、化学放射線療法をすべきか2017

    • Author(s)
      江口 英利, 後藤 邦仁, 和田 浩志, 浅岡 忠史, 野田 剛広, 山田 大作, 岩上 佳史, 川本 弘一, 森 正樹, 土岐 祐一郎
    • Organizer
      日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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