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Simultaneous development of novel treatment and companion biomarker of colorectal cancer based on CTOS method

Research Project

Project/Area Number 18K07926
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKyoto University

Principal Investigator

Jumpei Kondo  京都大学, 医学研究科, 特定助教 (80624593)

Co-Investigator(Kenkyū-buntansha) 井上 正宏  京都大学, 医学研究科, 特定教授 (10342990)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords大腸癌 / オルガノイド / 薬剤感受性 / バイオマーカー / 多様性 / BMP / MEK阻害 / 併用療法 / ERK阻害 / 3次元培養 / スクリーニング
Outline of Final Research Achievements

Drug sensitivity assay using colorectal CTOS suggested that BMP inhibitor is a candidate for a novel drug in a portion of colorectal cancer cases. Constitutive inactivation of BMP/SMAD pathway as well as lack of autocrine BMP ligands might be the cause of insufficient effect of BMP inhibitor. BMP inhibition suppressed MEK/ERK pathway in sensitive cases. Combination effect was observed with MEK inhibitor, but not with cetuximab, both in vitro and in vivo xenograft experiments. In vitro sensitivity assay results, which well correlated with in vivo effect of BMP/MEK inhibition is suggested to be a potential functional biomarker.

Academic Significance and Societal Importance of the Research Achievements

CTOSを用いた薬剤感受性アッセイ、移植腫瘍治療などにより、新規治療法の候補が導出された。またIn vitroでのCTOSを用いた感受性アッセイは、機能的バイオマーカーとして有用な可能性が示唆された。さらに、併用効果をもたらす分子機序およびバイオマーカー開発に向け、取得したデータの解析を継続することで、より有効な治療法や患者選択に繋がると期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (3 results) Book (1 results)

  • [Int'l Joint Research] Vanderbilt Uniersity(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] A smooth muscle‐derived, Braf ‐driven mouse model of gastrointestinal stromal tumor ( GIST ): evidence for an alternative GIST cell‐of‐origin2020

    • Author(s)
      Kondo Jumpei、Huh Won Jae、Franklin Jeffrey L、Heinrich Michael C、Rubin Brian P、Coffey Robert J
    • Journal Title

      The Journal of Pathology

      Volume: 252 Issue: 4 Pages: 441-450

    • DOI

      10.1002/path.5552

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Small subset of Wnt‐activated cells is an initiator of regrowth in colorectal cancer organoids after irradiation2020

    • Author(s)
      Endo Hiroko、Kondo Jumpei、Onuma Kunishige、Ohue Masayuki、Inoue Masahiro
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 12 Pages: 4429-4441

    • DOI

      10.1111/cas.14683

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel ex vivo disease model for extramammary Paget's disease using the cancer tissue-originated spheroid method2020

    • Author(s)
      Takahiro Arita, Jumpei Kondo, Yuka Kaneko, Miho Tsutsumi, Mai Kanemaru, Mari Matsui, Yukiyasu Arakawa, Norito Katoh, Masahiro Inoue, Jun Asai
    • Journal Title

      Journal of Dermatological Science

      Volume: 99(3) Issue: 3 Pages: 185-192

    • DOI

      10.1016/j.jdermsci.2020.07.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dedifferentiation of neuroendocrine carcinoma of the uterine cervix in hypoxia2020

    • Author(s)
      Kubota Satoshi、Tanaka Mie、Endo Hiroko、Ito Yu、Onuma Kunishige、Ueda Yutaka、Kamiura Shoji、Yoshino Kiyoshi、Kimura Tadashi、Kondo Jumpei、Inoue Masahiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 524 Issue: 2 Pages: 398-404

    • DOI

      10.1016/j.bbrc.2020.01.024

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrodynamic stress stimulates growth of cell clusters via the ANXA1/PI3K/AKT axis in colorectal cancer2019

    • Author(s)
      Hagihara Takeshi、Kondo Jumpei、Endo Hiroko、Ohue Masayuki、Sakai Yoshiharu、Inoue Masahiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-019-56739-7

    • NAID

      120006888522

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of Cancer Organoid Model for Drug Screening and Personalized Therapy2019

    • Author(s)
      Kondo Jumpei、Inoue Masahiro
    • Journal Title

      Cells

      Volume: 8 Issue: 5 Pages: 470-470

    • DOI

      10.3390/cells8050470

    • NAID

      120006777066

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-throughput screening in colorectal cancer tissue-originated spheroids2018

    • Author(s)
      Kondo Jumpei、Ekawa Tomoya、Endo Hiroko、Yamazaki Kanami、Tanaka Norio、Kukita Yoji、Okuyama Hiroaki、Okami Jiro、Imamura Fumio、Ohue Masayuki、Kato Kikuya、Nomura Taisei、Kohara Arihiro、Mori Seiichi、Dan Shingo、Inoue Masahiro
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 1 Pages: 345-355

    • DOI

      10.1111/cas.13843

    • NAID

      120006547404

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] BMP inhibition suppresses colorectal cancer growth via negative regulation of EGFR2021

    • Author(s)
      S Shimizu, J Kondo, M Inoue
    • Organizer
      第30回日本がん転移学会学術集会・総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Heterogeneous response to the blockade of BMP pathway in colorectal cancer2020

    • Author(s)
      S Shimizu, J Kondo, M Inoue
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Heterogeneous response to the blockade of BMP pathway in combination with RAS/MEK inhibition in colorectal cancer2018

    • Author(s)
      Jumpei Kondo
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Book] 患者由来がんモデルを用いたがん研究実践ガイド2019

    • Author(s)
      近藤純平、井上正宏 (佐々木 博己編)
    • Total Pages
      294
    • Publisher
      羊土社
    • ISBN
      9784758122429
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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