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Targeted therapy for salivary gland cancer stem cells

Research Project

Project/Area Number 21K16845
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionNational Hospital Organization, Kyushu Cancer Center (2022-2023)
Kyushu University (2021)

Principal Investigator

Nakano Takafumi  独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 客員研究員 (20770100)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords唾液腺癌 / 頭頸部癌 / 癌幹細胞 / 分子標的治療
Outline of Research at the Start

高悪性度唾液腺癌は、解剖学的な複雑さに起因する手術困難な場合が多く、遠隔転移症例は予後不良である事が多い。更に、有効な化学療法は殆ど存在しない。その原因として、唾液腺癌癌幹細胞がこれまでの化学療法に抵抗性である事が挙げられる。しかし、従来の唾液腺癌治療・研究では癌幹細胞の存在を考慮されずに行われており、癌幹細胞(CSC)と癌幹細胞以外の癌細胞(non-CSC)を個別に治療のターゲットとした研究はない。本申請研究は、唾液腺癌CSCを直接のターゲットとした治療とnon-CSCをターゲットとした既存の化学療法と併用する事で唾液腺癌の化学療法抵抗性を克服する新たな治療戦略の確立を目指すものである。

Outline of Final Research Achievements

We retrospectively reviewed the medical records of patients who were diagnosed with salivary gland cancer or head and neck cancer at the Kyushu University Hospital and National Kyushu Cancer Center. We revealed that most salivary gland cancers were positive for EGFR expression by IHC but that EGFR-targeting by the EXTREME regimen showed
little efficacy. We also showed tolerability and efficacy of immune checkpoint inhibitors (ICIs) for advanced-stage head and neck cancer patients. In particular, we also revealed tolerability and efficacy of ICIs for nasopharyngeal carcinoma patients, for which there have been insufficient data to date, also shows ICIs could be a good treatment option for this type of cancer.

Academic Significance and Societal Importance of the Research Achievements

唾液腺癌の有効な治療法は手術療法のみであり、遠隔転移を有する症例に対しては有効な全身治療選択肢や十分な予後マーカーは未解明である。唾液腺癌でEGFRは高頻度に発現していることを多数の症例で示せたことは、今後の治療ターゲットになり得ることを示したため意義深い。更に、上咽頭癌を除く頭頸部癌で有効性が証明されていた免疫チェックポイント阻害薬を含む治療レジメンも、上咽頭癌でも忍容性・有効性を明らかにした。手術困難例が多く、転移しやすい上咽頭癌に対して有効な治療選択肢が増えたことも非常に意義深いと考えられる。

Report

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

    (20 results)

All 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (12 results) (of which Int'l Joint Research: 3 results) Funded Workshop (1 results)

  • [Journal Article] Immune Checkpoint Inhibitors for Nasopharyngeal Carcinoma in a Real-world Setting in Japan2023

    • Author(s)
      MANAKO TOMOMI、YASUMATSU RYUJI、NAKANO TAKAFUMI、MATSUO MIOKO、TAKEUCHI TORANOSHIN、TAURA MASAHIKO、TAMAE AKIHIRO、YAMAUCHI MORIYASU、MASUDA MUNEYUKI、TAGUCHI KENICHI、NAKAGAWA TAKASHI
    • Journal Title

      In Vivo

      Volume: 37 Pages: 747-755

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Real-world Experience With Pembrolizumab for Advanced-stage Head and Neck Cancer Patients: A Retrospective, Multicenter Study2022

    • Author(s)
      NAKANO TAKAFUMI、YASUMATSU RYUJI、HASHIMOTO KAZUKI、KUGA RYOSUKE、HONGO TAKAHIRO、YAMAMOTO HIDETAKA、MATSUO MIOKO、WAKASAKI TAKAHIRO、JIROMARU RINA、MANAKO TOMOMI、TOH SATOSHI、MASUDA MUNEYUKI、YAMAUCHI MORIYASU、KURATOMI YUICHIRO、TAURA MASAHIKO、TAKEUCHI TORANOSHIN、NAKAGAWA TAKASHI
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 7 Pages: 3653-3664

    • DOI

      10.21873/anticanres.15854

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer2022

    • Author(s)
      NAKANO TAKAFUMI、YASUMATSU RYUJI、HASHIMOTO KAZUKI、KUGA RYOSUKE、HONGO TAKAHIRO、et al.
    • Journal Title

      In Vivo

      Volume: 36 Issue: 2 Pages: 979-984

    • DOI

      10.21873/invivo.12790

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A clinical analysis of oropharyngeal squamous cell carcinoma: a single-institution’s experience2022

    • Author(s)
      Jiromaru Rina、Yasumatsu Ryuji、Yamamoto Hidetaka、Kuga Ryosuke、Hongo Takahiro、Nakano Takafumi、Manako Tomomi、Hashimoto Kazuki、Wakasaki Takahiro、Matsuo Mioko、Nakagawa Takashi
    • Journal Title

      European Archives of Oto-Rhino-Laryngology

      Volume: Publish Ahead of Print Issue: 7 Pages: 1-9

    • DOI

      10.1007/s00405-021-07236-z

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Programmed Death‐Ligand 1 Expression and Tumor‐Infiltrating Lymphocytes in Temporal Bone Squamous Cell Carcinoma2021

    • Author(s)
      Hongo Takahiro、Kuga Ryosuke、Miyazaki Masaru、Komune Noritaka、Nakano Takafumi、Yamamoto Hidetaka、Koike Kensuke、Sato Kuniaki、Kogo Ryunosuke、Nabeshima Kazuki、Oda Yoshinao、Nakagawa Takashi
    • Journal Title

      The Laryngoscope

      Volume: 131 Issue: 12 Pages: 2674-2683

    • DOI

      10.1002/lary.29689

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] p16 Overexpression and Rb Loss Correlate with High‐risk HPV Infection in Oropharyngeal Squamous Cell Carcinoma2021

    • Author(s)
      Jiromaru Rina、Yamamoto Hidetaka、Yasumatsu Ryuji、Hongo Takahiro、Nozaki Yui、Nakano Takafumi、Hashimoto Kazuki、Nakagawa Takashi、Oda Yoshinao
    • Journal Title

      Histopathology

      Volume: in print Issue: 3 Pages: 358-369

    • DOI

      10.1111/his.14337

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 仰臥位で聴力が改善した外リンパ瘻の1例2021

    • Author(s)
      中野貴史、久保和彦、吉田崇正、小出彩佳、中川尚志
    • Journal Title

      耳鼻と臨床

      Volume: 67 Pages: 381-385

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Environment-induced YAP1 transcriptional reprogramming drives head and neck cancer2023

    • Author(s)
      Masuda M,Omori H,Sato K ,Nakano T,Penninger J,Gutkind J.S
    • Organizer
      7thWorld Congress of the International Federation of Head and Neck Oncologie Societies
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Environment-induced YAP1 transcriptional reprogramming drives head and neck cancer2023

    • Author(s)
      Masuda M,OmoriH,Sato K,Nakano T,Penninger J,Gutkind S
    • Organizer
      AACR-AHNS Head and Neck Cancer Conference:Innovationg Through Basic,Clinical and Translational Researc
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] YAP1-induced transcriptional reprogramming drives symbiotic evolution of head and neck cancer2023

    • Author(s)
      Masuda M,OmoriH,Sato K,Nakano T,Penninger J,Gutkind S
    • Organizer
      AHNS 11thInternational Conference on Head & Neck Cancer
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗アンドロゲン療法が奏効した脳転移を伴うHER2陰性唾液腺導管癌の一例2023

    • Author(s)
      薦田正人、中野 貴史、藤 賢史、花村文康、奥村祐太、西嶋智洋、益田 宗幸、江崎泰斗
    • Organizer
      日本臨床腫瘍学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Chemoradieselectionによる頭頸部癌治療強度の至適化前向き研究2022

    • Author(s)
      益田 宗幸, 宮城 慎平, 黒木 圭二, 佐藤 晋彰, 中野 貴史, 力丸 文秀, 藤 賢史, 國武 直信, 檜垣 雄一郎
    • Organizer
      日本頭頸部癌学会
    • Related Report
      2022 Research-status Report
  • [Presentation] YAP1/PITX2によって誘導される頭頸部扁平上皮癌の転写リプログラミング機構の解明2022

    • Author(s)
      佐藤 晋彰, 中野 貴史, 大森 裕文, 中川 尚志, 益田 宗幸
    • Organizer
      日本頭頸部癌学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Pembrolizumabの投与を行った甲状腺粘表皮癌の一例2022

    • Author(s)
      宮城 慎平, 中野 貴史, 藤原 義宜, 黒木 圭二, 原 大貴, 佐藤 晋彰, 力丸 文秀, 藤 賢史, 檜垣 雄一郎, 益田 宗幸
    • Organizer
      日本頭頸部癌学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 当科で施行したリンパ節生検症例の検討2022

    • Author(s)
      久保 和彦, 脇園 貴裕, 中野 貴史, 小出 彩佳, 吉田 崇正, 園田 世里夏, 友延 恵理, 中川 尚志
    • Organizer
      日本耳鼻咽喉科頭頸部外科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 上咽頭癌に対する免疫チェックポイント阻害薬の効果について2022

    • Author(s)
      真子 知美, 中野 貴史, 松尾 美央子, 竹内 寅之進, 田浦 政彦, 玉江 昭裕, 山内 盛泰, 倉富 勇一郎, 益田 宗幸, 田口 健一, 安松 隆治, 中川 尚志
    • Organizer
      日本耳鼻咽喉科頭頸部外科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] HMB配合製剤よるCRT誘発粘膜炎抑制効果の第2相ランダム化比較試験2022

    • Author(s)
      黒木 圭二、中野 貴史、力丸 文秀、藤 賢史、檜垣 雄一郎、益田 宗幸
    • Organizer
      日本頭頸部外科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 粘表皮癌癌幹細胞に対するmTOR阻害薬を用いた治療効果の検討2021

    • Author(s)
      中野貴史、益田宗幸、K.A.Warner、A.E.Oklejas、Z.Zhang、C.R.Ramirez、A.G.Shuman、J.E.Nor、安松隆治、中川尚志
    • Organizer
      第45回頭頸部癌学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 多形腺腫由来癌肉腫の1例2021

    • Author(s)
      中野 貴史, 久保 和彦, 園田 世里夏, 友延 恵理, 中川 尚志
    • Organizer
      第122回耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2021 Research-status Report
  • [Funded Workshop] AHNS10thInternational Conference2021

    • Related Report
      2021 Research-status Report

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

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