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Novel Biomarker for Therapeutic Target in Lung squamous cell carcinoma

Research Project

Project/Area Number 19K07706
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionGunma University

Principal Investigator

Rokudai Susumu  群馬大学, 大学院医学系研究科, 講師 (20392334)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsp53 / p63 / 肺がん / 扁平上皮がん / 扁平上皮癌 / がん関連繊維芽細胞 / 白血病 / がん抑制遺伝子 / がん遺伝子 / Lung Cancer / Squamous Cell Carcinoma / Squamous cell carcinoma / TP53 / TP63 / Syntaxin Binding Protein / Lung cancer
Outline of Research at the Start

扁平上皮がんは有効な分子標的が少ないために難治療性である。肺扁平上皮がんの診断マーカーであるTP63は腫瘍性に関与していると考えられるが、その詳細な仕組みは解明されていない。これまでに申請者は、肺がんにおける新たながん悪性化遺伝子として、SNAREタンパクであるSTXBP遺伝子を同定し、p63の発現制御とがん悪性化に関与する仕組みを明らかにした。本研究は、p63やSTXBPの詳細ながん悪性化機構を解明し、バイオマーカーや分子標的治療の探索を行う。
本研究は、さらにp63関連遺伝子による扁平上皮がんの発生や進行について詳細を解明し、バイオマーカー探索、新規分子標的治療としての展開を目的とする。

Outline of Final Research Achievements

Lung squamous cell carcinoma is difficult to treat because molecular targeted therapies are not effective. The disruption of control of the ΔNp63 gene expression, which is a diagnostic marker for squamous cell carcinoma, is one of the causes of cancer development and progression. Through comprehensive screening using a next-generation sequencer, we clarified the molecular mechanism that causes the disruption of p63 expression control related to poor prognosis, and clarified the mechanism involved in malignant transformation of cancer. In addition, in squamous cell carcinoma of the head and neck, AKT3 in cancer-related fibroblastic cells (CAF) was revealed to be associated with immunosuppression of the microenvironment of CAF, and is a potential biomarker of CAF activity and immunosuppressive microenvironment. Possibly a therapeutic target that inhibits the tumor-promoting function of CAF.

Academic Significance and Societal Importance of the Research Achievements

肺扁平上皮がんの診断マーカーでもあるΔNp63の発現の増加は高頻度で認められ、90%以上の扁平上皮がんで陽性であり、p53のがん抑制機能を阻害することで、がんの発生や進行、治療への抵抗性を高めるものと考えられており、治療標的としての可能性を秘めていると考えられる。本研究では、p63遺伝子の制御に関与するがんの発生や進行の詳細な仕組みを解明し、分子標的治療の開発に繋がる可能性を検討した。p63の発現制御機構を利用した化合物スクリーニングを進めており、アカデミア創薬としての開発が期待される。

Report

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

    (26 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (8 results) Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (4 results) (of which Invited: 1 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 3 results)

  • [Int'l Joint Research] コロンビア大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] セントジョンズ大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ペンシルバニア大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] リエージュ大学(ベルギー)

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

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] St John's University(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Pennsylvania(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Mon Pellie University(フランス)

    • Related Report
      2019 Research-status Report
  • [Journal Article] KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs2022

    • Author(s)
      Yan F, Li J, Milosevic J, Petroni R, Liu S, Shi Z, Yuan S, Reynaga JM, Qi Y, Rico J, Yu S, Liu Y, Rokudai S, Palmisiano N, Meyer SE, Sung PJ, Wan L, Lan F, Garcia BA, Stanger BZ, Sykes DB, Blanco MA.
    • Journal Title

      Cancer Discovery

      Volume: 12 Issue: 3 Pages: 792-811

    • DOI

      10.1158/2159-8290.cd-20-1459

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation2021

    • Author(s)
      Wang Herui、Li Bin、Asha Kulsum、Pangilinan Ryan L.、Thuraisamy Asha、Chopra Harman、Rokudai Susumu、Yu Yong、Prives Carol L.、Zhu Yan
    • Journal Title

      Journal of Biological Chemistry

      Volume: 297 Issue: 5 Pages: 101292-101292

    • DOI

      10.1016/j.jbc.2021.101292

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] AKT3 is a key regulator of head and neck squamous cell carcinoma. Takahashi H, Rokudai S, Kawabata-Iwakawa R, Sakakura K, Oyama T, Nishiyama M, Chikamatsu K.2021

    • Author(s)
      Takahashi H, Rokudai S, Kawabata-Iwakawa R, Sakakura K, Oyama T, Nishiyama M, Chikamatsu K.
    • Journal Title

      Cancer Science

      Volume: - Issue: 6 Pages: 2325-2334

    • DOI

      10.1111/cas.14911

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] AKT3 is a novel regulator of cancer-associated fibroblasts in head and neck squamous cell carcinoma2021

    • Author(s)
      Takahashi H, Rokudai S, Kawabata-Iwakawa R, Sakakura K, Oyama T, Nishiyama M, Chikamatsu K.
    • Journal Title

      Cancers

      Volume: 13(6) Issue: 6 Pages: 1233-1233

    • DOI

      10.3390/cancers13061233

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Syntaxin binding proten 4 as a novel therapeutic target and an effective biomarker for better treatment selection in lung squamous cell carcinoma.2020

    • Author(s)
      Bilguun EO, Kaira K, Kawabata-Iwakawa R, Rokudai S, Shimizu K, Yokobori T, Oyama T, Shirabe K, Nishiyama M.
    • Journal Title

      Research Square, Review

      Volume: -

    • DOI

      10.21203/rs.3.rs-39783/v1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinctive roles of syntaxin binding protein 4 and its action target, TP63, in lung squamous cell carcinoma: A theranostic study for the precision medicine2020

    • Author(s)
      Bilguun EO, Kaira K, Kawabata-Iwakawa R, Rokudai S, Shimizu K, Yokobori T, Oyama T, Shirabe K, Nishiyama M.
    • Journal Title

      BMC Cancer

      Volume: 20(1) Pages: 1-14

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-Throughput RNA Interference Screen Targeting Synthetic-Lethal Gain-of-Function of Oncogenic Mutant TP53 in Triple-Negative Breast Cancer.2020

    • Author(s)
      Rokudai S.
    • Journal Title

      Methods Mol Diol.

      Volume: 2108 Pages: 297-303

    • DOI

      10.1007/978-1-0716-0247-8_25

    • ISBN
      9781071602461, 9781071602478
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Carbonic anhydrase 9 expression is associated with poor prognosis, tumor proliferation, and radiosensitivity of thymic carcinomas.2019

    • Author(s)
      Ohtaki Y, Shimizu K, Kawabata-Iwakawa R, Gombodorj N, Altan B, Rokudai S, Yamane A, Kaira K, Yokobori T, Nagashima T, Obayashi K, Nakazawa S, Iijima M, Kosaka T, Yajima T, Mogi A, Kuwano H, Shirabe K, Nishiyama M.
    • Journal Title

      Oncotarget

      Volume: 10(13) Issue: 13 Pages: 1306-1319

    • DOI

      10.18632/oncotarget.26657

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 肺腺癌におけるアロマターゼの意義と細胞増殖能への影響2021

    • Author(s)
      大和田 竜司、矢澤理麻、調憲、六代範
    • Organizer
      日本がん分子標的治療学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Novel Biomarker and Development of Squamous Cell Carcinoma for and Development of Therapeutic Target2019

    • Author(s)
      Susumu Rokudai, Kyoichi Kaira, Daiki Tanaka, Eisuke Horigome, Michiru Fujieda, Yukihiro Otaka, Misaki Iijima, Yuji Kumakura, Kimihiro Shimizu, Tetsunari Oyama, Jun’ichi Tamura, Ken Shirabe, Carol Prives, Masahiko Nishiyama
    • Organizer
      第57回日本癌治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 扁平上皮がんにおける新規p63結合分子STXBP4による腫瘍悪性化とがん分子行的薬の探索2019

    • Author(s)
      六代範, 田中大暉, 杉本明生、堀込瑛介、藤枝みちる、熊倉祐二、清水公裕、調憲, 西山正彦
    • Organizer
      第78回 日本癌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 扁平上皮がんにおける新規p63結合分子STXBP4によるがん分子行的薬の探索2019

    • Author(s)
      六代 範, 堀込瑛介, 田中大暉, 調憲, 桑野博行, 西山正彦
    • Organizer
      第23回 日本がん分子標的治療学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Book] High-Throughput RNA Interference Screen Targeting Synthetic-Lethal Gain-of-Function of Oncogenic Mutant TP53 in Triple-Negative Breast Cancer (Reviews).2020

    • Author(s)
      Rokudai S.
    • Publisher
      Springer Nature
    • Related Report
      2020 Research-status Report
  • [Remarks] 「扁平上皮がんにおけるp63を標的とする分子治療薬の探索」(国立研究開発法人日本医療研究開発機構)

    • URL

      https://www.amed.go.jp/content/000095508.pdf

    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] Method for manufacturing peripheral nerve cells2021

    • Inventor(s)
      高橋寛之、西山正彦、六代範、吉山伸司
    • Industrial Property Rights Holder
      高橋寛之、西山正彦、六代範、吉山伸司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抹消神経細胞の製造方法」2021

    • Inventor(s)
      高橋寛之、西山正彦、六代範、吉山伸司
    • Industrial Property Rights Holder
      高橋寛之、西山正彦、六代範、吉山伸司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Acquisition Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] Method for manufacturing peripheral nerve cells.2020

    • Inventor(s)
      西山正彦、六代範、吉山伸司
    • Industrial Property Rights Holder
      西山正彦、六代範、吉山伸司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] iPS抹消神経細胞の製造方法2019

    • Inventor(s)
      西山正彦、六代範、吉山伸司
    • Industrial Property Rights Holder
      西山正彦、六代範、吉山伸司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
    • Overseas

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Published: 2019-04-18   Modified: 2025-01-30  

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