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Development of novel therapeutics that utilize driver oncogene-induced senescence

Research Project

Project/Area Number 18H02819
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionNagoya University

Principal Investigator

Sato Mitsuo  名古屋大学, 医学系研究科(保健), 教授 (70467281)

Co-Investigator(Kenkyū-buntansha) 長谷 哲成  名古屋大学, 医学部附属病院, 助教 (30621635)
湯川 博  名古屋大学, 未来社会創造機構, 招へい教員 (30634646)
田中 一大  名古屋大学, 医学部附属病院, 病院助教 (40809810)
芳川 豊史  名古屋大学, 医学系研究科, 教授 (00452334)
川口 晃司  名古屋大学, 医学部附属病院, 病院准教授 (10402611)
川井 久美  名古屋大学, 医学系研究科(保健), 准教授 (50362231)
横井 香平  名古屋大学, 医学系研究科, 教授 (60378007)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywords変異KRAS / 細胞老化 / 肺癌 / 創薬 / 創薬研究 / ドライバー癌遺伝子 / ドライバー遺伝子
Outline of Final Research Achievements

The purpose of this study was to develop a treatment for mutant KRAS based on the phenomenon of oncogene-induced cellular senescence (OIS) that inhibits proliferation. Using an immortalized normal human bronchial epithelial cell line that expresses mutant KRAS under the control, we performed a pooled shRNA library screening. Gene X was identified as a promising target, followed by high-throughput screening with a compound library to identify multiple candidate compounds that inhibit gene X. However, we stopped the project because of difficulty in developing a further assay system to evaluate inhibitory efficacy of identified compound.

Academic Significance and Societal Importance of the Research Achievements

変異KRASは固形癌において最も高頻度なドライバー癌遺伝子である。ドライバー癌遺伝子は癌細胞の増殖や生存に必須とされ、有効な治療標的となる。本課題は、未だ高い効果を示す治療が開発されていない変異KRAS肺癌の治療開発に取り組んだ。成果として治療標的候補遺伝子Xを特定し、同遺伝子の阻害作用を示すコンパウンドも特定した。変異KRAS癌の治療開発に役立つ知見を得たと考える。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (5 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results)

  • [Journal Article] Phenotypic screening using large-scale genomic libraries to identify drug targets for the treatment of cancer2020

    • Author(s)
      Mitsuo Sato
    • Journal Title

      Oncol Lett

      Volume: 19 Pages: 3617-3626

    • DOI

      10.3892/ol.2020.11512

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immortalized normal human lung epithelial cell models for studying lung cancer biology2020

    • Author(s)
      Sato M, Shay JW, Minna JD.
    • Journal Title

      Respir Investig

      Volume: 58 Issue: 5 Pages: 344-354

    • DOI

      10.1016/j.resinv.2020.04.005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] UHRF1, a Regulator of Methylation, as a Diagnostic and Prognostic Marker for Lung Cancer2020

    • Author(s)
      Goto Daiki、Komeda Kazuki、Uwatoko Natsuki、Nakashima Moeka、Koike Mayu、Kawai Kaho、Kodama Yuta、Miyazawa Ayako、Tanaka Ichidai、Hase Tetsunari、Morise Masahiro、Hasegawa Yoshinori、Kawabe Tsutomu、Sato Mitsuo
    • Journal Title

      Cancer Investigation

      Volume: 38 Issue: 4 Pages: 240-249

    • DOI

      10.1080/07357907.2020.1747483

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemotherapy Induced Changes to Fibrin Clots Properties in Lung Cancer: Is It Favorable?2019

    • Author(s)
      Mitsuo Sato
    • Journal Title

      J Thorac Dis .

      Volume: 11(Suppl 9)

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific copy number changes as potential predictive markers for adjuvant chemotherapy in non-small cell lung cancer2018

    • Author(s)
      Mitsuo Sato
    • Journal Title

      Transl Lung Cancer Res.

      Volume: 7(Suppl 4) Issue: S4 Pages: S346-S348

    • DOI

      10.21037/tlcr.2018.11.04

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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