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Identification of molecular targets by analysis of signaling networks in pancreatic cancer

Research Project

Project/Area Number 16H05165
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionTohoku University (2017-2020)
Tokyo Women's Medical University (2016)

Principal Investigator

Furukawa Toru  東北大学, 医学系研究科, 教授 (30282122)

Co-Investigator(Kenkyū-buntansha) 樋口 亮太  東京女子医科大学, 医学部, 講師 (20318059)
Project Period (FY) 2016-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords膵臓癌 / 膵頭領域癌 / オルガノイド / 全エクソン解析 / 分子標的 / ドライバー分子 / インテグリン結合キナーゼ / intern-linked kinase / 膵臓がん / 信号伝達経路 / 膵頭領域がん / エクソーム / 細胞培養 / 癌 / 培養 / 分子ネットワーク / オミックス解析
Outline of Final Research Achievements

We aimed to establish a system for identifying and testing genotype-oriented targeted drugs for pancreatobiliary cancers by combining exome sequencing and organoid culture of primary tumors. Tumor cells isolated from resected tumors were subjected to organoid cultures. Exome sequencing was performed on the primary tumors. Genotype-oriented candidate targeted drugs were identified from the exome sequencing and their efficacies were tested in the organoids. Organoid cultures were succeeded in 30 of 54 (55.6%) cases. Exome sequencing revealed a variety of somatic mutations. Some of the aberrations were candidates for targeted therapies. Integrin-linked kinase (ILK) was a novel candidate target, and an ILK inhibitor was confirmed to suppress proliferation of patient-derived organoids. By combining exome sequencing and organoid culture, our model enabled to identify genotype-oriented targets for personalized medicine and to test efficacies of candidate targeted drugs in the organoids.

Academic Significance and Societal Importance of the Research Achievements

癌の診療では腫瘍のゲノム解析から個々の癌に適した分子標的を見出し治療することが行われるが、見出した分子標的が実際に患者由来の癌に対し効果を示すか検証できるシステムがなかった。本研究では難治性である膵臓・膵頭領域癌について、癌オルガノイド培養と網羅的遺伝子解析を組み合わせることにより、実際に患者由来検体で分子標的治療の効果を確認できる個別化医療システムを構築した。また、膵臓・膵頭領域癌に対する新規分子治療標的としてILKを同定した。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018 2017 2016 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (16 results) (of which Int'l Joint Research: 7 results,  Invited: 10 results) Remarks (1 results)

  • [Journal Article] Development of a system combining comprehensive genotyping and organoid cultures for identifying and testing genotype-oriented personalised medicine for pancreatobiliary cancers2021

    • Author(s)
      Shiihara Masahiro、Ishikawa Tomohiko、Saiki Yuriko、Omori Yuko、Hirose Katsuya、Fukushige Shinichi、Ikari Naoki、Higuchi Ryota、Yamamoto Masakazu、Morikawa Takanori、Nakagawa Kei、Hayashi Hiroki、Mizuma Masamichi、Ohtsuka Hideo、Motoi Fuyuhiko、Unno Michiaki、Okamura Yasunobu、Kinoshita Kengo、Furukawa Toru
    • Journal Title

      European Journal of Cancer

      Volume: 148 Pages: 239-250

    • DOI

      10.1016/j.ejca.2021.01.047

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas2021

    • Author(s)
      Kobayashi Toshikazu、Omori Yuko、Ono Yusuke、Karasaki Hidenori、Mizukami Yusuke、Makino Naohiko、Motoi Fuyuhiko、Unno Michiaki、Ueno Yoshiyuki、Furukawa Toru
    • Journal Title

      Journal of Gastroenterology

      Volume: Online ahead of print Issue: 6 Pages: 581-592

    • DOI

      10.1007/s00535-021-01783-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 膵癌のゲノム異常2019

    • Author(s)
      古川徹
    • Journal Title

      肝胆膵

      Volume: 79 Pages: 1117-1123

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 膵癌・胆道癌におけるprecision medicineの現況2019

    • Author(s)
      古川徹
    • Journal Title

      肝胆膵

      Volume: 78 Pages: 759-763

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 日本人の膵癌におけるゲノム解析2019

    • Author(s)
      古川徹
    • Journal Title

      胆と膵

      Volume: 40 Pages: 287-290

    • Related Report
      2019 Annual Research Report
  • [Presentation] 胆膵領域における炎症と発癌2020

    • Author(s)
      古川徹
    • Organizer
      第28回日本消化器関連学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Organoid培養と遺伝子解析を用いた膵胆道癌の個別化医療モデルの確立2020

    • Author(s)
      椎原正尋、石川智彦、碇直樹、樋口亮太、元井冬彦、山本雅一、海野 倫明、古川徹
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] IPMN組織亜型における遺伝子異常についての相互関係の分子病理学的解析2020

    • Author(s)
      小林敏一、大森優子、小野裕介、水上裕輔、牧野直彦、元井冬彦、海野倫明、上野義之、古川徹
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Development of a system combining comprehensive genotyping and organoid cultures for identifying and testing genotype oriented personalized medicine for pancreatobiliary cancers.2019

    • Author(s)
      Shiihara M, Ishikawa T, Ikari N, Higuchi R, Yazawa T, Uemura S, Izumo W, Yamamoto M, Motoi F, Morikawa T, Nakagawa K, Hayashi H, Mizuma M, Otsuka H, Ishida M, Masuda K, Kawaguchi K, Ariake K, Takadate T, Iseki M, Hata T, Unno M, Furukawa T.
    • Organizer
      50th Anniversary Meeting of American Pancreatic Association and Japan Pancreas Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Variations in IPMN and their clinicopathological relevance.2019

    • Author(s)
      Furukawa T.
    • Organizer
      2019 Meeting of the International Association of Pancreatology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 膵腫瘍のゲノム解析とゲノム医療2019

    • Author(s)
      古川徹
    • Organizer
      北信オンコロジーセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 膵臓腫瘍の発生進展機構の解明2019

    • Author(s)
      古川徹
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膵臓腫瘍の発生進展機構の解明2018

    • Author(s)
      古川徹
    • Organizer
      第29回日本消化器癌発生学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Targeting MAPK/ERK and Its Downstream in Pancreatic Cancer.2018

    • Author(s)
      Furukawa T.
    • Organizer
      4th ARO-Japan and TSPA/TCTC-Taiwan Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathobiology of intraductal neoplasms of the pancreas.2018

    • Author(s)
      Furukawa T.
    • Organizer
      Pancreas2018 (Baltimore)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Clinicopathological relevance of SMAD4 and RUNX3 in pancreatic cancer.2018

    • Author(s)
      Hirose K, Furukawa T
    • Organizer
      Pancreas2018 (Baltimore)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵腫瘍のゲノム解析2018

    • Author(s)
      古川徹
    • Organizer
      第49回日本膵臓学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 早期膵癌の定義と分子基盤について2018

    • Author(s)
      古川徹
    • Organizer
      第56回日本癌治療学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Signaling aberrations and their implications in pancreatic cancer.2017

    • Author(s)
      Furukawa Toru
    • Organizer
      2017 Asan Pancreatic Cancer Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas.2017

    • Author(s)
      古川 徹
    • Organizer
      第48回日本膵臓学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Subtype classification of IPMN and its impact on patient care.2016

    • Author(s)
      Furukawa T.
    • Organizer
      American Pancreatic Association Pre-Meeting “IPMN: Beyond Guidelines and Treatment.”
    • Place of Presentation
      Boston, MA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 患者由来のミニ癌(癌オルガノイド)を利用した個別化医療

    • URL

      https://www.tohoku.ac.jp/japanese/newimg/pressimg/tohokuuniv-press20210322_01web_cancer.pdf

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2022-12-28  

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