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Establishment of molecular simulation with mathematical model to enable the selection of molecular target drugs for lung cancer.

Research Project

Project/Area Number 21K12110
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionUniversity of Toyama

Principal Investigator

Takaoka Yutaka  富山大学, 学術研究部医学系, 教授 (20332281)

Co-Investigator(Kenkyū-buntansha) 菅野 亜紀  富山大学, 学術研究部医学系, 特命助教 (20457039)
永野 達也  神戸大学, 医学研究科, 講師 (80624684)
大田 美香  富山大学, 学術研究部医学系, 特命助教 (20274706)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsEGFR-TKI / 分子標的薬 / 分子シミュレーション / バイオインフォマティクス / EGFRチロシンキナーゼ阻害剤 / 薬効予測
Outline of Research at the Start

本研究は、計算機を用いて抗がん剤治療の薬効を予測可能にする研究であり、研究成果を臨床現場の治療への利用が可能な世界初の研究である。肺がん細胞で新規変異体の発見が続くEGFRに対して、分子標的薬(EGFR-TKI)の中から治療薬の選択を実現する。

Outline of Final Research Achievements

We examined the hypothesis that there are amino acid substitutions outside the known mutation sites for single and multiple mutations of the EGFR dimer, and reported that erlotinib is effective for both L858R and A871G mutations, but not for patients with multiple mutations of L858R and A871G,Molecular simulations were able to reproduce these results. In addition, it was also confirmed that this molecular analysis methods can be applied to the research of numerous pathological process.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的・社会的意義は、肺がんの分子標的薬のEGFR-TKI世代別にin silico薬効予測を可能にすることである。特に肺がん細胞で新規変異体の発見が続くEGFRから、抗がん剤選択の基準を提供する点は意義深い。薬効予測の実現により副作用の少ない効率的・効果的で安全な医療を実現する。またこの研究で得られた成果は、あらゆる分子標的薬の評価や創薬にも応用可能で、波及効果は大きい。また解析技術基盤としては、病態研究への応用が可能である。

Report

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

    (21 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Remarks (1 results)

  • [Int'l Joint Research] Queen Mary University of London(英国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production2023

    • Author(s)
      Wu Xilin、Azizan Elena A. B.、Murakami Masanori、Beuschlein Felix、Ito Akihiko、Brown Morris J, et al.
    • Journal Title

      Nature Genetics

      Volume: 55 Issue: 6 Pages: 1009-1021

    • DOI

      10.1038/s41588-023-01403-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prediction of visceral pleural invasion of clinical stage I lung adenocarcinoma using thoracoscopic images and deep learning2023

    • Author(s)
      Shimada Yoshifumi、Ojima Toshihiro、Takaoka Yutaka、Sugano Aki、Someya Yoshiaki、Hirabayashi Kenichi、Homma Takahiro、Kitamura Naoya、Akemoto Yushi、Tanabe Keitaro、Sato Fumitaka、Yoshimura Naoki、Tsuchiya Tomoshi
    • Journal Title

      Surgery Today

      Volume: 未巻 Issue: 6 Pages: 540-550

    • DOI

      10.1007/s00595-023-02756-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In silico binding affinity of the spike protein with ACE2 and the relative evolutionary distance of S gene may be potential factors rapidly obtained for the initial risk of SARS-CoV-22023

    • Author(s)
      Sugano Aki、Murakami Junon、Kataguchi Haruyuki、Ohta Mika、Someya Yoshiaki、Kimura Shigemi、Kanno Akira、Maniwa Yoshimasa、Tabata Toshihide、Tobe Kazuyuki、Takaoka Yutaka
    • Journal Title

      Microbial Risk Analysis

      Volume: 25 Pages: 100278-100278

    • DOI

      10.1016/j.mran.2023.100278

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential Contribution of Cell Adhesion Molecule 1 to the Binding of SARS-CoV-2 Spike Protein to Mouse Nasal Mucosa.2023

    • Author(s)
      Takeuchi F, Sugano A, Yoneshige A, Hagiyama M, Inoue T, Wada A, Takaoka Y, Ito A.
    • Journal Title

      Cells Tissues Organs

      Volume: Online ahead of print. Issue: 4 Pages: 1-12

    • DOI

      10.1159/000534892

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of infectivity of SARS-CoV2: Mathematical model with analysis of docking simulation for spike proteins and angiotensin-converting enzyme 22022

    • Author(s)
      Takaoka Yutaka、Sugano Aki、Morinaga Yoshitomo、Ohta Mika、Miura Kenji、Kataguchi Haruyuki、Kumaoka Minoru、Kimura Shigemi、Maniwa Yoshimasa
    • Journal Title

      Microbial Risk Analysis

      Volume: 22 Pages: 100227-100227

    • DOI

      10.1016/j.mran.2022.100227

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SARS-CoV-2 Omicron BA.2.75 Variant May Be Much More Infective than Preexisting Variants Based on In Silico Model.2022

    • Author(s)
      Sugano Aki、Takaoka Yutaka、Kataguchi Haruyuki、Ohta Mika、Kimura Shigemi、Araki Masatake、Morinaga Yoshitomo、Yamamoto Yoshihiro
    • Journal Title

      Microorganisms

      Volume: 10 Issue: 10 Pages: 2090-2090

    • DOI

      10.3390/microorganisms10102090

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increase in the number and duration of sleep episodes during class after reopening of schools following closure due to COVID-19.2022

    • Author(s)
      Shigemi Kimura, Yutaka Takaoka, Aki Sugano
    • Journal Title

      Kobe Journal of Medical Sciences

      Volume: 68

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Indigo Plant Leaf Extract Inhibits the Binding of SARS-CoV-2 Spike Protein to Angiotensin-Converting Enzyme 22022

    • Author(s)
      Hagiyama M, Takeuchi F, Sugano A, Yoneshige A, Inoue T, Wada A , Kajiyama H, Takaoka Y, Sasaki K, Ito A
    • Journal Title

      Exp Ther Med

      Volume: 23 Issue: 4 Pages: 274-274

    • DOI

      10.3892/etm.2022.11200

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Silico Drug Repurposing by Structural Alteration after Induced Fit: Discovery of a Candidate Agent for Recovery of Nucleotide Excision Repair in Xeroderma Pigmentosum Group D Mutant (R683W)2021

    • Author(s)
      Takaoka Yutaka、Ohta Mika、Tateishi Satoshi、Sugano Aki、Nakano Eiji、Miura Kenji、Suzuki Takashi、Nishigori Chikako
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 3 Pages: 249-249

    • DOI

      10.3390/biomedicines9030249

    • NAID

      120007026365

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genotype-phenotype correlation in WT1 exon 8 to 9 missense variants2021

    • Author(s)
      China Nagano, Yutaka Takaoka, Koichi Kamei, Riku Hamada, Daisuke Ichikawa, Kazuki Tanaka, Yuya Aoto, Shinya Ishiko, Rini Rossanti, Nana Sakakibara, Eri Okada, Tomoko Horinouchi, Tomohiko Yamamura, Yurika Tsuji, Yuko Noguchi, Shingo Ishimori, Hiroaki Nagase, Takeshi Ninchoji, Kazumoto Iijima, Kandai Nozu
    • Journal Title

      Kidney International Reports

      Volume: - Issue: 8 Pages: 2114-2121

    • DOI

      10.1016/j.ekir.2021.05.009

    • NAID

      120007140164

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Core body temperature changes in school-age children with circadian rhythm sleep?wake disorder2021

    • Author(s)
      Kimura Shigemi、Takaoka Yutaka、Toyoura Makiko、Kohira Shinji、Ohta Mika
    • Journal Title

      Sleep Medicine

      Volume: 87 Pages: 97-104

    • DOI

      10.1016/j.sleep.2021.08.026

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 仮説検証から予測確認へのパラダイムシフト: in silico解析のヘルスケアへの展開2023

    • Author(s)
      高岡 裕
    • Organizer
      第43回和漢医薬学総合研究所特別セミナー 『富山大学―熊本大学連携による持続可能なグローバルヘルスケア研究拠点の形成』
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 病態の分子シミュレーション解析系確立と計算創薬教育基盤の整備2023

    • Author(s)
      高岡 裕
    • Organizer
      Toyama Academic GALA 2023
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 検証から予測へ:分子シミュレーションと数理モデルによる漢方薬の薬物有害反応解析2023

    • Author(s)
      高岡 裕
    • Organizer
      第13回 日本中医薬学会シンポジウム「伝統医学を科学する」
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Prediction research for the bio process by the homology modeling and molecular dynamics simulation - from Verification to Prediction2023

    • Author(s)
      Yutaka TAKAOKA
    • Organizer
      MOE Symposium 2023
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Prediction for Adverse Reaction and Efficacy of Medicine by Molecular Dynamics Simulation - from Verification to Prediction -2023

    • Author(s)
      Yutaka TAKAOKA
    • Organizer
      The 7th Toyama-Basel Joint Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 分子シミュレーション解析による腸間膜静脈硬化症の病因予測2023

    • Author(s)
      大田美香、菅野亜紀、高岡 裕
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 構造解析と多変量解析を用いたWT1遺伝子exon 8-9ミスセンス変異における臨床症状予測2023

    • Author(s)
      染谷芳明、長野智那、大田美香、菅野亜紀、野津寛大、高岡 裕
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] SARS-Cov-2スパイクタンパクのACE2 in silico結合能とS遺伝子進化距離による感染リスクの予測2023

    • Author(s)
      菅野亜紀、村上純音、片口治幸、大田美香、木村重美、高岡 裕
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Remarks] 富山大学先端抗体医薬雨開発センター・バイオインフォマティクス部門

    • URL

      https://www.antibody.u-toyama.ac.jp/team/bioinformatics/

    • Related Report
      2022 Research-status Report

URL: 

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

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