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Molecular basis for the cross-sectional vulnerability of various cancers elicited by atypical nucleic acid configuration and its therapeutic application

Research Project

Project/Area Number 18K19487
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

Seimiya Hiroyuki  公益財団法人がん研究会, がん化学療法センター 分子生物治療研究部, 部長 (50280623)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsグアニン4重鎖 / がん細胞 / 薬剤感受性 / 核酸 / グアニン4重鎖
Outline of Final Research Achievements

Some types of cancer cells exhibit significant vulnerability to stabilization of G-quadruplex (G4), an atypical higher-order structure of nucleic acids. However, the molecular mechanism for such selective anti-proliferative effect remains elusive. In this study, we performed comparative analyses on G4-stabilizing chemical (G4 ligand)-sensitive and resistant cancer cells and identified ABCG2, a member of the ABC transporter family, as a resistant factor to a synthetic G4 ligand. Furthermore, we identified a candidate gene X, which knockdown by siRNAs alleviates resistance of cancer cells to G4 ligands.

Academic Significance and Societal Importance of the Research Achievements

がん薬物療法を発達させるうえで、革新的新薬の創製と精度の高い効果予測法の確立が求められている。神経膠芽腫および膵がんはいずれも難治がんの代表格であり、これらの新薬開発は喫緊の課題である。本研究は、G4リガンドが神経膠芽腫に加えてある種の膵がんにも有効な創薬シーズである可能性を示した。さらに、本研究で同定されたG4リガンド感受性規定候補因子が同剤の治療効果を予測するバイオマーカーとなる可能性が示唆された。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (36 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (22 results) (of which Int'l Joint Research: 6 results,  Invited: 15 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Universite Claude Bernard Lyon1(フランス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] アラバマ大学バーミングハム校(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] G-quadruplex in cancer biology and drug discovery.2020

    • Author(s)
      Nakanishi C, Seimiya H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: In press Issue: 1 Pages: 45-50

    • DOI

      10.1016/j.bbrc.2020.03.178

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] From the wings to the center stage of chromosomes.2019

    • Author(s)
      Okamoto K, Seimiya H.
    • Journal Title

      J Biol Chem

      Volume: 294 Issue: 47 Pages: 17723-17724

    • DOI

      10.1074/jbc.h119.011587

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Revisiting Telomere Shortening in Cancer.2019

    • Author(s)
      Keiji Okamoto and Hiroyuki Seimiya
    • Journal Title

      Cells

      Volume: 8 Issue: 2 Pages: 107-107

    • DOI

      10.3390/cells8020107

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells2018

    • Author(s)
      Fujiwara C, Muramatsu Y, Nishii M, Tokunaka K, Tahara H, Ueno M, Yamori T, Sugimoto Y, Seimiya H8
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41598-018-33139-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of G-quadruplex ligands for selective induction of a parallel-type topology2018

    • Author(s)
      Ma Yue、Tsushima Yamato、Sakuma Mai、Sasaki Shogo、Iida Keisuke、Okabe Sachiko、Seimiya Hiroyuki、Hirokawa Takatsugu、Nagasawa Kazuo
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 16 Issue: 40 Pages: 7375-7382

    • DOI

      10.1039/c8ob01702f

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Telomere as the starting point of anticancer drug discovery2020

    • Author(s)
      Seimiya H.
    • Organizer
      LyonSE&N - ELyT Workshop 2020
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腫瘍形成におけるインターフェロン標的遺伝子ISG15の機能解明2020

    • Author(s)
      犬山慶輔、 岡本啓治、右田敏郎、藤原理恵、清宮啓之
    • Organizer
      文部科学省新学術領域研究 学術研究支援基盤形成 先端モデル動物支援プラットフォーム 2019年度成果発表会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Tankyrase and G-quadruplex as molecular targets for cancer therapy2019

    • Author(s)
      Seimiya H.
    • Organizer
      第25回日本遺伝子細胞治療学会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Telomere as the starting point of anticancer drug discovery2019

    • Author(s)
      Seimiya H.
    • Organizer
      The 7th Symposium, RIKEN-Max Planck Joint Research Center
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 四重鎖核酸ケモプローブに対する細胞応答の解明とがん創薬への応用2019

    • Author(s)
      清宮啓之
    • Organizer
      第92回日本生化学会大会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Crossroads of telomere biology and cancer drug discovery2019

    • Author(s)
      Seimiya H.
    • Organizer
      第78回日本癌学会学術総会コアシンポジウム
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] テロメアから始まるがん創薬2019

    • Author(s)
      清宮啓之
    • Organizer
      JSPS「日本におけるケミカルバイオロジーの新展開」 に関する産学協力研究委員会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] がんにおけるテロメア短縮のパラドクスを再考する2019

    • Author(s)
      岡本啓治、清宮啓之
    • Organizer
      第42回日本分子生物学会年会ワークショップ
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 分子プロファイリング支援活動のご紹介 ~小さな分子を起点とした生命科学研究のお手伝い2019

    • Author(s)
      清宮啓之
    • Organizer
      文部科学省新学術領域研究 学術研究支援基盤形成 先端モデル動物支援プラットフォーム 2019年度若手支援技術講習会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] テロメア非コードRNAとがん2019

    • Author(s)
      清宮啓之
    • Organizer
      JARIランチョンセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Wnt/G4を標的としたがん創薬2019

    • Author(s)
      清宮啓之
    • Organizer
      広島大学大学院医系科学研究科セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 染色体の末端から始まるがん創薬2019

    • Author(s)
      清宮啓之
    • Organizer
      徳島大学大学院医歯薬学研究部 呼吸器・膠原病内科学分野 開講48周年記念会 篠原 勉先生 特任教授就任祝賀会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 制がん性グアニン四重鎖リガンドの新たな作用機序の解明2019

    • Author(s)
      岡部幸子、岡本啓治、新家一男、旦 慎吾、長澤和夫、清宮啓之
    • Organizer
      第23回日本がん分子標的治療学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] テロメア長による遺伝子発現制御と腫瘍形態への影響2019

    • Author(s)
      岡本啓治、清宮啓之
    • Organizer
      第23回日本がん分子標的治療学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] プロテオーム解析による制がん性グアニン四重鎖リガンドの標的分子の探索2019

    • Author(s)
      中西忠也、岡部幸子、岡本啓治、小林美月、新家一男、長澤和夫、清宮啓之
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] グアニン四重鎖リガンドによるミトコンドリア遺伝子の発現制御2019

    • Author(s)
      岡部幸子、井上直、村松由起子、新家一男、長澤和夫、清宮啓之
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Telomere as the starting point of anticancer drug discovery2019

    • Author(s)
      Hiroyuki Seimiya
    • Organizer
      11th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: Biology to Precision Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] グアニン4重鎖安定化物質の分子プロファイリングとがん創薬への展開2019

    • Author(s)
      清宮啓之、新家一男、長澤和夫
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Targeting glioma stem cells by pharmacological stabilization of G-quadruplexes2018

    • Author(s)
      Sachiko Okabe, Takahiro Nakamura, Daiki Hasegawa, Reina Kojima, Keiji Okamoto, Ichiro Nakano, Kazuo Shin-ya, Kazuo Nagasawa, Hiroyuki Seimiya
    • Organizer
      AACR Annual Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] G-quadruplex nucleic acids as a molecular target for cancer therapy2018

    • Author(s)
      Hiroyuki Seimiya, Kazuo Shin-ya, Kazuo Nagasawa
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] New mode-of-action of a telomerase inhibitor MST-312 and modifiers of its anticancer efficacy2018

    • Author(s)
      藤原千明、村松由起子、矢守隆夫、杉本芳一、清宮啓之
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] G-quadruplex as a molecular target for cancer therapy2018

    • Author(s)
      Hiroyuki Seimiya
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 進化するがん創薬2019

    • Author(s)
      清宮啓之(編)
    • Total Pages
      344
    • Publisher
      化学同人
    • ISBN
      4759817336
    • Related Report
      2019 Annual Research Report
  • [Book] 決定版 阻害剤・活性化剤ハンドブック2019

    • Author(s)
      新家一男、清宮啓之(秋山徹、河府和義 編)
    • Total Pages
      648
    • Publisher
      羊土社
    • ISBN
      9784758120999
    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      https://www.jfcr.or.jp/chemotherapy/department/molecular_biotherapy/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      https://www.jfcr.or.jp/chemotherapy/department/molecular_biotherapy/index.html

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] がんを治療するための組み合わせ物及び医薬組成物2020

    • Inventor(s)
      長澤和夫、松田未沙子、馬悦、清宮啓之
    • Industrial Property Rights Holder
      国立大学法人東京農工大学,公益財団法人がん研究会
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-008592
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗がん剤2019

    • Inventor(s)
      長澤和夫、松田未沙子、馬悦、清宮啓之
    • Industrial Property Rights Holder
      国立大学法人東京農工大学,公益財団法人がん研究会
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抗膵がん剤2018

    • Inventor(s)
      長澤和夫、松田未沙 子、馬悦、清宮啓之
    • Industrial Property Rights Holder
      東京農工大学、 がん研究会
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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