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Establishment of a mouse model of Oct4-positive lung cancer stem cells and development of innovative therapies to eradicate cancer stem cells

Research Project

Project/Area Number 22K19529
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionOkayama University

Principal Investigator

Ohashi Kadoaki  岡山大学, 大学病院, 准教授 (60729193)

Co-Investigator(Kenkyū-buntansha) 木浦 勝行  岡山大学, 医学部, 客員研究員 (10243502)
片山 量平  公益財団法人がん研究会, がん化学療法センター 基礎研究部, 部長 (60435542)
Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2022: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords非小細胞癌 / 癌幹細胞 / Oct4 / 非小細胞肺癌 / EGFR変異 / 2型肺胞上皮細胞 / 肺癌 / Oct4 / 2型肺胞上皮細胞 / 腫瘍微小環境
Outline of Research at the Start

上皮成長因子受容体(EGFR)遺伝子変異を有する肺癌(EGFR肺癌)は、非喫煙者に発生する肺腺癌の半数以上を占めるが、薬物療法で根治できない。多分化能をもつ癌幹細胞(cancer stem cells:CSCs)が根治の障壁の一因とされるが、CSCsのin vivoモデルは確立していない。CSCsの病態および腫瘍微小環境(TME : tumor microenvironment)の間質細胞・免疫細胞との相互関係についても未解明である。
CSCsに対する革新的治療の開発に向け、マウスモデルを用いCSCsおよびTMEのCSCsへの関与について病態の解明、新規治療標的の同定を目指す。

Outline of Final Research Achievements

Cancer stem cells (CSCs) have attracted attention as a cause of lung cancer that cannot be cured by drug therapy, but their pathogenesis is not yet understood. The aim of this study was to establish a mouse model of CSCs and to identify novel therapeutic targets against CSCs. Possible CSCs were selected from the lung tumors of the crossbred mice using Oct4 as a marker, and their characteristics as CSCs, such as viability and multidrug resistance, were evaluated. In addition, we will attempt to identify novel therapeutic targets in CSCs and their tumor microenvironment by gene expression analysis.

Academic Significance and Societal Importance of the Research Achievements

上皮成長因子受容体遺伝子変異を有する肺癌(EGFR肺癌)は、非喫煙者に発生する肺腺癌の半数以上を占める非常に重要な疾患であるが、薬物療法での根治は困難である。免疫チェックポイント阻害薬など腫瘍免疫療法の効果が乏しいタイプであることも知られており、根治を目指す治療戦略の標的として、多分化能と多剤薬剤耐性能を持つ癌幹細胞(cancer stem cells:CSCs)の病態を探索することは、革新的な治療法の確立につながる可能性があり非常に意義が高い。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (10 results)

All 2023 2022

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (4 results)

  • [Journal Article] PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer2023

    • Author(s)
      Nakasuka Takamasa、Ohashi Kadoaki、Nishii Kazuya、Hirabae Atsuko、Okawa Sachi、Tomonobu Nahoko、Takada Kenji、Ando Chihiro、Watanabe Hiromi、Makimoto Go、Ninomiya Kiichiro、Fujii Masanori、Kubo Toshio、Ichihara Eiki、Hotta Katsuyuki、Tabata Masahiro、Kumon Hiromi、Maeda Yoshinobu、Kiura Katsuyuki
    • Journal Title

      Lung Cancer

      Volume: 178 Pages: 1-10

    • DOI

      10.1016/j.lungcan.2023.01.018

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies2023

    • Author(s)
      Kemmotsu N , Ninomiya K , Kunimasa K , IshinoT ,Nagasaki J , Otani Y , Michiue H ,Ichihara E ,Ohashi K ,Inoue T ,Tamiya M ,Sakai K ,Ueda Y , Dansako H ,Nishio K ,Kiura K , Date I ,Togashi Y
    • Journal Title

      International Journal of Cancer

      Volume: 154(1) Issue: 1 Pages: 169-179

    • DOI

      10.1002/ijc.34700

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer.2023

    • Author(s)
      Ando C, Ichihara E, Nishi T, Morita A, Hara N, Takada K, Nakasuka T, Watanabe H, Kano H, Nishii K, Makimoto G, Kondo T, Ninomiya K, Fujii M, Kubo T, Ohashi K, Matsuoka KI, Hotta K, Tabata M, Maeda Y, Kiura K.
    • Journal Title

      Cancer Sci.

      Volume: 114 Issue: 11 Pages: 4343-4354

    • DOI

      10.1111/cas.15958

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer2023

    • Author(s)
      Hara Naofumi、Ichihara Eiki、Kano Hirohisa、Ando Chihiro、Morita Ayako、Nishi Tatsuya、Okawa Sachi、Nakasuka Takamasa、Hirabae Atsuko、Abe Masaya、Asada Noboru、Ninomiya Kiichiro、Makimoto Go、Fujii Masanori、Kubo Toshio、Ohashi Kadoaki、Hotta Katsuyuki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
    • Journal Title

      Translational Lung Cancer Research

      Volume: 12 Issue: 10 Pages: 2098-2112

    • DOI

      10.21037/tlcr-23-99

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survival Mechanisms of Drug Tolerant Persister Cancer Cells against Targeted Anticancer Drugs2023

    • Author(s)
      Taoka M, Makimoto G, Ohashi K.
    • Journal Title

      Gan To Kagaku Ryoho.

      Volume: 50(12) Pages: 1239-1245

    • Related Report
      2023 Annual Research Report
  • [Journal Article] CD8+ T-cell responses are boosted by dual PD-1/VEGFR2 blockade after EGFR inhibition in Egfrmutant lung cancer.2022

    • Author(s)
      Nishii K, Ohashi K, Tomida S, Nakasuka T, Hirabae A,Okawa S, Nishimura J, Higo H, Watanabe H, Kano H, Ando C, Makimoto G, Ninomiya K, Kato Y, Kubo T, Ichihara E, Hotta K, Tabata M, Toyooka S, Udono H, Maeda Y, Kiura K.
    • Journal Title

      Cancer Immunol Res.

      Volume: 10 Issue: 9 Pages: 1111-1126

    • DOI

      10.1158/2326-6066.cir-21-0751

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Egfr改変肺癌マウスモデルを用いたosimertinibとnintedanibによる抗腫瘍効果の検討2023

    • Author(s)
      栗林忠弘, 大橋圭明, 田岡征高, 森田絢子, 西達也, 西村淳, 大川祥, 中須賀崇匡, 平生敦子, 二宮貴一朗, 槇本剛, 藤井昌学, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行.
    • Organizer
      第64回日本肺癌学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Egfr肺癌に対しADU-S100はosimertinibが誘導する抗腫瘍免疫を増強する2023

    • Author(s)
      西村淳, 大橋圭明, 栗林忠弘, 田岡征高, 大川祥, 中須賀崇匡, 西井和也, 平生敦子, 二宮貴一朗, 槇本剛, 藤井昌学, 市原英基,頼冠名, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行.
    • Organizer
      第64回日本肺癌学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] EGFR阻害が誘導するEgfr肺癌に対する抗腫瘍免疫を逐次的VEGFR-2/PD-1阻害が増強する2022

    • Author(s)
      西井和也,大橋圭明,冨田秀太,中須賀崇匡,平生敦子,大川祥, 西村淳,安東千裕,槇本剛,二宮貴一朗,加藤有加,久保寿夫, 市原英基,堀田勝幸,田端雅弘,豊岡伸一,鵜殿平一郎,前田嘉信,木浦勝行
    • Organizer
      第63回日本肺癌学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Egfr変異陽性肺癌に対する Ad-SGE-REICと抗PD-1抗体併用による抗腫瘍免疫賦活効果2022

    • Author(s)
      中須賀崇匡,大橋圭明,西井和也,平生敦子,大川祥,髙田健二,西村淳,栗林忠弘,安東千裕, 西達也,森田絢子,槇本剛,二宮貴一朗,藤井昌学,市原英基,堀田勝幸,田端雅弘,前田嘉信,木浦勝行
    • Organizer
      第63回日本肺癌学会学術集会
    • Related Report
      2022 Research-status Report

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Published: 2022-07-05   Modified: 2025-01-30  

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