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Clinicopathological characterization and therapeutic proposals for tuft cell-like thoratic cancers

Research Project

Project/Area Number 21K06902
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKyoto University

Principal Investigator

Yosuke Yamada  京都大学, 医学研究科, 講師 (40742622)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsタフト (tuft) 細胞 / 塩類細胞 / 胸腺がん / 胸腺腫 / 肺がん / 乳がん / Tuft細胞性がん / Tuft細胞 / POU2F3 / FOXI1
Outline of Research at the Start

代表的な胸部がんである胸腺がんおよび肺がんにはいずれも、悪性度が高く、かつ有効な治療法が確立されていない一群が存在する。本研究の目的は、tuft細胞性を示す胸腺がんおよび肺がんの詳細な臨床病理学的特徴を単施設の症例を用いて探索し、tuft細胞性が当該腫瘍の臨床病理像に与える影響を明らかにすることである。このことで、胸腺がんや肺がんのより妥当な病理組織学的分類、適切な治療指針の確立に寄与することが期待される。

Outline of Final Research Achievements

We explored the clinicopathological features of tumors with tuft cell-like expression profiles, mainly focusing on thymic and lung cancers. As representative achievements, we found that tuft cell-like lung cancers also exhibit gene expression profiles of ionocytes, another rare epithelial cell type, and that tuft cell-like small cell lung carcinomas are sensitive to PARP and BCL2 co-inhibition. Furthermore, we proposed that "tuft cell-like" carcinomas are present in multiple organs, with unique biological features, and that tuft cells may be physiologically present in organs where they have not been previously known to exist.

Academic Significance and Societal Importance of the Research Achievements

正常のtuft細胞の機能は2016年頃より、tuft細胞に類似した発現プロファイルを示すがん腫は2018年に報告されたばかりで、tuft細胞や "tuft細胞様" がんの特性は未だ十分には明らかになっていない。本助成事業に係る一連の研究は、胸部腫瘍を中心としつつ、全身のtuft細胞様がんの認識やその特性の解明に寄与した点で学術的意義がある。加えて、tuft細胞様がんのユニークな薬剤感受性を明らかにした点で、研究成果には社会的意義もあると考える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (28 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (9 results) Journal Article (10 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results)

  • [Int'l Joint Research] University of Hamburg/Heidelberg University/University of Goettingen(ドイツ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Heidelberg University/University of Gottingen/University Medical Center Hamburg(ドイツ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Cornell University/Indiana University(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Medical University of Vienna(オーストリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University Hospital of Pisa(イタリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Heidelberg University/University of Gottingen/University Medical Center Hamburg(ドイツ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Cornell University(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Medical University of Vienna(オーストリア)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University Hospital of Pisa(イタリア)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Expression of FOXI1 and POU2F3 varies among different salivary gland neoplasms and is higher in Warthin tumor2024

    • Author(s)
      Hoki Masahito、Yamada Yosuke、Hiratomo Emi、Hirata Masahiro、Takeuchi Yasuhide、Yoshimatsu Masayoshi、Kikuchi Masahiro、Kishimoto Yo、Marx Alexander、Haga Hironori
    • Journal Title

      Discover Oncology

      Volume: 15 Issue: 1 Pages: 36-36

    • DOI

      10.1007/s12672-024-00892-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular Pathology/Genetics of Thymic Tumors: extended abstract2024

    • Author(s)
      Yosuke Yamada、Alexander Marx
    • Journal Title

      Mediastinum(受理)

      Volume: X

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX92023

    • Author(s)
      Yamada Yosuke、Simon Ronald、Iwane Kosuke、Nakanishi Yuki、Takeuchi Yasuhide、Yoshizawa Akihiko、Takada Masahiro、Toi Masakazu、Haga Hironori、Marx Alexander、Sauter Guido
    • Journal Title

      BMC Cancer

      Volume: 23 Issue: 1 Pages: 438-438

    • DOI

      10.1186/s12885-023-10949-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histogenetic and disease‐relevant phenotypes in thymic epithelial tumors (TETs): The potential significance for future TET classification2023

    • Author(s)
      Yamada Yosuke
    • Journal Title

      Pathology International

      Volume: 73 Issue: 7 Pages: 265-280

    • DOI

      10.1111/pin.13343

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathological snapshots of thymic epithelial tumors with invasion into neighboring structures: preparing for the forthcoming revision of the TNM classification2023

    • Author(s)
      Yamada Yosuke、Haga Hironori
    • Journal Title

      Mediastinum

      Volume: 7 Pages: 36-36

    • DOI

      10.21037/med-23-28

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thymic Carcinoma: Unraveling Neuroendocrine Differentiation and Epithelial Cell Identity Loss2023

    • Author(s)
      Yamada Yosuke、Iwane Kosuke、Nakanishi Yuki、Haga Hironori
    • Journal Title

      Cancers

      Volume: 16 Issue: 1 Pages: 115-115

    • DOI

      10.3390/cancers16010115

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor2023

    • Author(s)
      Fujii Hirotake、Yamada Yosuke、Yamamura Kentaro、Ishida Yoshihiro、Tsujimura Marina、Matsumoto Kazuhisa、Tanaka Satona、Date Hiroshi、Nishikawa Tadaaki、Yoshida Yukihiro、Kashima Jumpei、Yatabe Yasushi、Ogawa Seishi、Marx Alexander、Ulbright Thomas M.、Haga Hironori
    • Journal Title

      Virchows Archiv

      Volume: 未定 Issue: 5 Pages: 923-927

    • DOI

      10.1007/s00428-023-03529-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tuft cell-like carcinomas: novel cancer subsets present in multiple organs sharing a unique gene expression signature2022

    • Author(s)
      Yamada Yosuke、Bohnenberger Hanibal、Kriegsmann Mark、Kriegsmann Katharina、Sinn Peter、Goto Norihiro、Nakanishi Yuki、Seno Hiroshi、Chigusa Yoshitsugu、Fujimoto Masakazu、Minamiguchi Sachiko、Haga Hironori、Simon Ronald、Sauter Guido、Str?bel Philipp、Marx Alexander
    • Journal Title

      British Journal of Cancer

      Volume: 127 Issue: 10 Pages: 1876-1885

    • DOI

      10.1038/s41416-022-01957-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pulmonary cancers across different histotypes share hybrid tuft cell/ionocyte-like molecular features and potentially druggable vulnerabilities2022

    • Author(s)
      Yosuke Yamada, Djeda Belharazem-Vitacolonnna, Hanibal Bohnenberger, Christel Weiss, Naoko Matsui, Mark Kriegsmann, Katharina Kriegsmann, Peter Sinn, Katja Simon-Keller, Gerhard Hamilton, Thomas Graeter, Gerhard Preissler, German Ott, et al.
    • Journal Title

      Cell Death Dis

      Volume: 13 Issue: 11 Pages: 979-979

    • DOI

      10.1038/s41419-022-05428-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] POU2F3 beyond thymic carcinomas: expression across the spectrum of thymomas hints to medullary differentiation in type A thymoma2022

    • Author(s)
      Yamada Yosuke、Sugimoto Akihiko、Hoki Masahito、Yoshizawa Akihiko、Hamaji Masatsugu、Date Hiroshi、Haga Hironori、Marx Alexander
    • Journal Title

      Virchows Archiv

      Volume: 480 Issue: 4 Pages: 843-851

    • DOI

      10.1007/s00428-021-03229-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Whether tuft cells are present in the human breast?: the potential relevance to triple-negative breast cancer2023

    • Author(s)
      Yosuke Yamada
    • Organizer
      Tuft Cells 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular Pathology/Genetics of Thymic Tumors2023

    • Author(s)
      Yosuke Yamada
    • Organizer
      13th International Thymic Malignancy Interest Group Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 胸腺扁平上皮がん2022

    • Author(s)
      山田 洋介
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 胸腺腫瘍のUp-to-date2022

    • Author(s)
      山田 洋介
    • Organizer
      第97回日本病理学会近畿支部学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Molecular Subsets of Thymic Squamous Cell Carcinoma2022

    • Author(s)
      Yosuke Yamada
    • Organizer
      IASLC 2022 Asia Conference on Lung Cancer (ACLC 2022)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 胸腺上皮性腫瘍における皮質上皮・髄質上皮マーカーの発現に関する検討2022

    • Author(s)
      山田 洋介
    • Organizer
      第68回日本病理学会秋期特別総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Pulmonary tuft cell-like cancers across different histotypes share molecular features with potentially druggable vulnerabilities2022

    • Author(s)
      Y. Yamada, H. Bohnenberger, M. Kriegsmann, K. Kriegsmann, S. Scholch, P. Strobel, A. Marx
    • Organizer
      The European Lung Cancer Congress (ELCC 2022)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pulmonary tuft cell-like cancers across different histotypes share molecular features with potentially druggable vulnerabilities2022

    • Author(s)
      Yosuke Yamada, Hanibal Bohnenberger, Mark Kriegsmann, Katharina Kriegsmann, Sebastian Scholch, Philipp Strobel, Alexander Marx
    • Organizer
      European Lung Cancer Congress 2022
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Thymic carcinomas with tuft cell-like phaenotype2021

    • Author(s)
      Yosuke Yamada
    • Organizer
      33rd European Congress of Pathology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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