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Establishing novel molecular-targeted cancer therapies based on molecular diagnostics focusing on prognostic factor CYLD

Research Project

Project/Area Number 18H02591
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionKumamoto University

Principal Investigator

Jono Hirofumi  熊本大学, 病院, 准教授 (40515483)

Co-Investigator(Kenkyū-buntansha) 齋藤 秀之  熊本大学, 病院, 教授 (40225727)
大槻 純男  熊本大学, 大学院生命科学研究部(薬), 教授 (60323036)
松井 啓隆  熊本大学, 大学院生命科学研究部(医), 教授 (60379849)
林 光博  国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (50735628)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
KeywordsCYLD / 個別化医療 / 分子標的治療薬 / 薬剤感受性
Outline of Final Research Achievements

For establishing novel molecular-targeted therapies for cancer patients with poor prognosis, we performed molecular pathological analysis focusing on the loss of prognostic factor CYLD expression, and investigated the usefulness of molecular diagnosis in molecular-targeted drug treatment. As a result, we revealed as follows: 1. Correlation between loss of CYLD expression and poor prognosis/drug sensitivity, 2. Mechanism of enhanced sensitivity to EGFR-targeted molecular medicine through EGFR over-activation, 3. loss of CYLD expression may serve as a biomarker for predicting various type of molecular-targeted medicine.

Academic Significance and Societal Importance of the Research Achievements

近年開発されているがん分子標的薬は、標的となる分子の診断(遺伝子変異など)により治療有効症例の判定が可能であり、がん患者の生命予後は改善されている。しかし、検査により「治療不応」と診断された患者は、対症療法・緩和ケアで余命を過ごすしか選択肢はない。本研究では、このような「治療不応」と診断された予後不良患者に新たな治療選択を提供することを目的に、生命予後規定因子として知られているCYLDという分子に着目した診断により、特定のがん分子標的が「治療不応」患者にも有効である可能性を示した。CYLD の分子診断に着目した本研究は、がん患者に多くの選択肢を提供し、がんの克服に貢献することが期待される。

Report

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

    (45 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (30 results) (of which Int'l Joint Research: 5 results,  Invited: 5 results) Book (1 results)

  • [Int'l Joint Research] Georgia State University(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Georgia State University(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Georgia State University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Georgia State University(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] The tumour suppressor CYLD is required for clathrin-mediated endocytosis of EGFR and cetuximab-induced apoptosis in head and neck squamous cell carcinoma.2022

    • Author(s)
      Liu R, Shinriki S, Maeshiro M, Hirayama M, Jono H, Yoshida R, Nakayama H, Matsui H
    • Journal Title

      Cancers

      Volume: 14 Issue: 1 Pages: 173-173

    • DOI

      10.3390/cancers14010173

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli2021

    • Author(s)
      Shirakawa Yuki、Ohta Kunimasa、Miyake Shunsuke、Kanemaru Ayumi、Kuwano Akari、Yonemaru Kou、Uchino Shota、Yamaoka Michiko、Ito Yuki、Ito Naofumi、Hide Takuichiro、Shinojima Naoki、Mukasa Akitake、Saito Hideyuki、Jono Hirofumi
    • Journal Title

      Cells

      Volume: 10 Issue: 11 Pages: 2970-2970

    • DOI

      10.3390/cells10112970

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CYLD: a novel stratification marker for malignant tumors2021

    • Author(s)
      Shunsuke Miyake, Ayumi Kanemaru, Hideyuki Saito, Hirofumi Jono
    • Journal Title

      Journal of Asian Association of Schools of Pharmacy

      Volume: 10 Pages: 17-22

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ribosomal protein S6 promotes stem‐like characters in glioma cells2020

    • Author(s)
      Shirakawa Yuki、Hide Takuichiro、Yamaoka Michiko、Ito Yuki、Ito Naofumi、Ohta Kunimasa、Shinojima Naoki、Mukasa Akitake、Saito Hideyuki、Jono Hirofumi
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 6 Pages: 2041-2051

    • DOI

      10.1111/cas.14399

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between clinicopathological characteristics and CYLD expression in patients with cholesteatoma.2020

    • Author(s)
      Miyake S, Miwa T, Yoneda G, Kanemaru A, Saito H, Minoda R, Orita Y, Saito H, Jono H.
    • Journal Title

      PLoS One

      Volume: 15

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The 2nd Symposium “Current Status of Reverse Translational Research Conducted by Hospital Pharmacists” ~Challenges for Screening of Therapeutic Molecular Target and Personalized Medicine~2019

    • Author(s)
      Masuda S, Itoh H, Ikeda R, Jono H
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 139 Issue: 6 Pages: 899-900

    • DOI

      10.1248/yakushi.18-00213-F

    • NAID

      130007657107

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2019-06-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of tumor suppressor CYLD expression triggers cisplatin resistance in oral squamous cell carcinoma.2019

    • Author(s)
      Suenaga N, Kuramitsu M, Komure K, Kanemaru A, Takano K, Ozeki K, Nishimura Y, Yoshida R, Nakayama H, Shinriki S, Saito H, Jono H.
    • Journal Title

      J Mol Sci

      Volume: 20 Issue: 20 Pages: 5194-5194

    • DOI

      10.3390/ijms20205194

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishing individualized medicine for intractable cancer based on clinical molecular pathogenesis -A novel predictive marker CYLD for molecular targeted therapies-2019

    • Author(s)
      Jono H, Saito H
    • Journal Title

      Proceedings for Annual Meeting of The Japanese Pharmacological Society

      Volume: 92 Issue: 0 Pages: 2-S15-4

    • DOI

      10.1254/jpssuppl.92.0_2-S15-4

    • NAID

      130007813106

    • ISSN
      2435-4953
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis2018

    • Author(s)
      Jono Hirofumi
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 138 Issue: 4 Pages: 451-455

    • DOI

      10.1248/yakushi.17-00207

    • NAID

      130006601922

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2018-04-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of CYLD promotes cell invasion via ALK5 stabilization in oral squamous cell carcinoma2018

    • Author(s)
      Shinriki S, Jono H, Maeshiro M, Nakamura T, Guo J, Li JD, Ueda M, Yoshida R, Shinohara M, Nakayama H, Matsui H, Ando Y.
    • Journal Title

      Journal of Pathology

      Volume: 244 Issue: 3 Pages: 367-379

    • DOI

      10.1002/path.5019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Novel roles of ribosomal protein S6 promotes development and maintenance of glioblastoma multiforme stem cells2022

    • Author(s)
      Hirofumi Jono, Yuki Shirakawa, Yuki Ito, Shunsuke Miyake, Ayumi Kanemaru, Takuichiro Hide, Akitake Mukasa, Kunimasa Ohta, Hideyuki Saito
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Novel roles of tumor suppressor CYLD in malignant characteristics of glioblastoma multiforme2021

    • Author(s)
      Hirofumi Jono, Yuki Ito, Michiko Yamaoka, Yuki Shirakawa, Takuichiro Hide, Hideyuki Saito
    • Organizer
      The 23rd Korea-Japan Joint Seminar on Pharmacology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 進行卵巣癌における腫瘍抑制遺伝子CYLD 発現低下の臨床的意義の解明2021

    • Author(s)
      松山果穂、三宅俊介、下村祐美、金丸歩美、西郷智香、成田勇樹、本岡大社、岩越裕、本原剛志、 片渕秀隆、齋藤秀之、城野博史
    • Organizer
      第61回日本臨床化学会年次学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] CYLD 発現低下による予後不良トリプルネガティブ型乳癌に対するNF-kB シグナル標的治療の有効性2021

    • Author(s)
      新垣ひとみ、桑野明香里、平井ちか、末永尚輝、金丸歩美、三宅俊介、林光博、成田勇樹、齋藤秀之、城野博史
    • Organizer
      第61回日本臨床化学会年次学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 真珠腫組織におけるCYLD 発現に着目した臨床病理学的解析2021

    • Author(s)
      三宅俊介、三輪徹、米田剛、金丸歩美、齋藤陽元、蓑田涼生、折田頼尚、齋藤秀之、城野博史
    • Organizer
      第61回日本臨床化学会年次学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 卵巣癌における腫瘍抑制遺伝子 CYLD 発現低下の臨床的・生物学的意義の解明2021

    • Author(s)
      三宅俊介、松山果穂、下村祐美、金丸歩美、西郷智香、本岡大社、岩越裕、本原剛志、片渕秀隆、齋藤秀之
    • Organizer
      第38回日本薬学会九州山口支部大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] リン酸化プロテオミクスを活用したCYLD発現低下・予後不良膠芽腫に対する新規治療標的の探索2021

    • Author(s)
      伊藤由貴、山岡道子、白川裕貴、増田豪、秀拓一郎、成田勇樹、齋藤秀之、城野博史
    • Organizer
      第74回薬理学会西南部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 卵巣癌における腫瘍抑制遺伝子CYLD発現消失の臨床薬理学的意義の解明2021

    • Author(s)
      三宅俊介、齋藤秀之、城野博史
    • Organizer
      第42回日本臨床薬理学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Biological significance of CYLD downregulation in Triple negative breast cancer.2021

    • Author(s)
      桑野明香里、平井ちか、末永尚輝、金丸歩美、新垣ひとみ、林光博、西郷智香、齋藤秀之、城野博史
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Biological significance of CYLD expression in malignant characteristics of glioblastoma multiforme2021

    • Author(s)
      伊藤由貴、山岡道子、白川裕貴、秀拓一郎、齋藤秀之、城野博史
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Personalized cancer therapy based on clinical molecular pathogenesis. - Clinical significance of tumor suppressor CYLD in malignant tumors -2020

    • Author(s)
      Hirofumi Jono
    • Organizer
      Asian Association of Schools of Pharmacy (AASP) Young Scientist Conference 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 非小細胞肺癌における腫瘍抑制遺伝子CYLD発現の予後・効果予測因子としての可能性の検証2020

    • Author(s)
      西村 優佳,髙野 佳奈子,末永 尚輝,三宅 俊介,金丸 歩美,齋藤 秀之,城野 博史
    • Organizer
      第73回薬理学会西南部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新規効果予測マーカー CYLD の分子診断を基軸とした新たながん分子標的治療の確立2019

    • Author(s)
      城野博史
    • Organizer
      第59回日本臨床化学会年次学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] トリプルネガティブ型乳癌の悪性化形質獲得における腫瘍抑制遺伝子CYLD発現低下の臨床的意義2019

    • Author(s)
      桑野明香里、平井ちか、末永尚輝、金丸歩美、三宅俊介、林光博、齋藤秀之、城野博史
    • Organizer
      第59回日本臨床化学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膠芽腫の薬物治療抵抗性におけるがん抑制遺伝子CYLD発現の意義2019

    • Author(s)
      山岡道子、白川裕貴、伊藤由貴、秀拓一郎、齋藤秀之、城野博史
    • Organizer
      医療薬学フォーラム2019 第27回クリニカルファーマシーシンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 口腔扁平上皮癌におけるがん抑制遺伝子CYLDの治療効果予測マーカーとしての有用性の検証2019

    • Author(s)
      小関利弥、末永尚輝、金丸歩美、高野佳奈子、西村優佳、齋藤秀之、城野博史
    • Organizer
      医療薬学フォーラム2019 第27回クリニカルファーマシーシンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 口腔癌におけるCYLD発現低下誘導性のシスプラチン耐性化機序の解明2019

    • Author(s)
      末永尚輝、金丸歩美、小関利弥、齋藤秀之、城野博史
    • Organizer
      医療薬学フォーラム2019 第27回クリニカルファーマシーシンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Loss of tumor suppressor CYLD expression induces cisplatin resistance in oral squamous cell carcinoma2019

    • Author(s)
      Suenaga N, Kanemaru A, Ozeki K, Saito H, Jono H
    • Organizer
      第29回日本医療薬学会年会(International symposium)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical significance of CYLD down-regulation in invasiveness of triple negative breast cancer2019

    • Author(s)
      Kuwano A, Hirai C, Suenaga N, Kanemaru A, Hayashi M, Saito H, Jono H
    • Organizer
      第29回日本医療薬学会年会(International symposium)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 口腔腔扁平上皮癌細胞の抗がん剤性感受性に対するがん抑制遺伝子CYLD発現低下の影響2019

    • Author(s)
      小関利弥、末永尚輝、金丸歩美、髙野佳奈子、西村優佳、齋藤秀之、城野博史
    • Organizer
      第36回日本薬学会九州支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Establishing individualized medicine for intractable cancer based on clinical molecular pathogenesis - A novel predictive marker CYLD for molecular targeted therapies -2019

    • Author(s)
      Jono H, Saito H
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 卵巣癌における腫瘍抑制遺伝子CYLDの発現消失はAktシグナルを介した悪性化形質獲得の要因となる2019

    • Author(s)
      三宅俊介、金丸歩美、高野佳奈子、西郷智香、本岡大社、本原剛志、齋藤秀之、城野博史
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 口腔癌における腫瘍抑制遺伝子 CYLD 発現の効果予測マーカーとしての有用性2019

    • Author(s)
      城野博史、高野佳奈子、西村優佳、末永尚輝、金丸歩美、三宅俊介、小関利弥、齋藤秀之
    • Organizer
      日本臨床腫瘍薬学会学術大会2019
    • Related Report
      2018 Annual Research Report
  • [Presentation] Loss of CYLD expression correlates with deep tumor invasion & poor prognosis in patients with invasive oral squamous cell carcinoma2018

    • Author(s)
      Jono H, Shinriki S, Suenaga N, Kanemaru A, Miyake S, Takano K, Yoshida S, Saito H
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 乳癌薬物療法に対する耐性獲得における生命予後規定因子 CYLD 発現低下の臨床的意義の解明2018

    • Author(s)
      城野博史、平井ちか、西郷智香、林光博、神力悟、安東由喜雄、齋藤秀之、岩瀬弘敬
    • Organizer
      医療薬学フォーラム2018 第26回クリニカルファーマシーシンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 進行卵巣癌における CYLD 発現変動の臨床的意義の解明および分子診断・個別化治療への応用可能性の検討2018

    • Author(s)
      三宅俊介、金丸歩美、髙野佳奈子、西郷智香、本岡大社、本原剛志、齋藤秀之、城野博史
    • Organizer
      日本臨床化学会第58回年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 乳癌薬物療法における腫瘍抑制遺伝子 CYLD 発現低下の臨床的意義の解明2018

    • Author(s)
      城野博史、平井ちか、西郷智香、林光博、神力悟、安東由喜雄、岩瀬弘敬、齋藤秀之
    • Organizer
      日本臨床化学会第58回年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Establishing individualized cancer therapy based on clinical molecular pathogenesis - Clinical significance of tumor suppressor CYLD down-regulation in malignant tumors2018

    • Author(s)
      Hirofumi Jono
    • Organizer
      第28回日本医療薬学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 乳癌薬物療法における腫瘍抑制遺伝子 CYLD 発現低下の臨床的意義の解明2018

    • Author(s)
      西郷智香、平井ちか、桑野明香里、林光博、岩瀬弘敬、齋藤秀之、城野博史
    • Organizer
      第28回日本医療薬学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腫瘍悪性化形質における腫瘍抑制遺伝子 CYLD 発現低下の生物学的意義の解明2018

    • Author(s)
      髙野佳奈子、西村優佳、末永尚輝、金丸歩美、三宅俊介、小関利弥、齋藤秀之、城野博史
    • Organizer
      第35回日本薬学会九州支部大会
    • Related Report
      2018 Annual Research Report
  • [Book] 図解 腫瘍薬学2020

    • Author(s)
      城野博史、三宅俊介
    • Total Pages
      677
    • Publisher
      南山堂
    • ISBN
      9784525721619
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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