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Development of synthetic lethal approach for treating solid tumors that have progressed despite chemoradiation therapy.

Research Project

Project/Area Number 23K21471
Project/Area Number (Other) 21H03070 (2021-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2021-2023)
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

小村 和正  大阪医科薬科大学, 医学部, 講師 (10789853)

Co-Investigator(Kenkyū-buntansha) 辻川 和丈  大阪大学, 大学院薬学研究科, 教授 (10207376)
東 治人  大阪医科薬科大学, 医学部, 教授 (40231914)
谷口 高平  大阪医科薬科大学, 医学部, 講師 (70779686)
吉見 昭秀  国立研究開発法人国立がん研究センター, 研究所, 分野長 (80609016)
松井 佑介  名古屋大学, 医学系研究科(保健), 准教授 (90761495)
Project Period (FY) 2021-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2025: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2024: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2023: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2021: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywords化学放射線療法 / がん / 耐性 / 腫瘍合成致死 / 薬剤耐性 / オミックスデータ
Outline of Research at the Start

継続課題の為、記入しない。

Outline of Annual Research Achievements

本研究では、申請者機関に特徴的な化学放射線療法施行症例でのオミックスデータ構築をまず大きなマイルストーンに設定し、研究を進めている。尿路上皮がん検体について、手術時からの臨床検体をRNA-later保存液保管としてバーコード管理を進めてきた。今回約500例でのリボソームRNA除去ライブラリーとwhole exome seq library作製を進めており、Novaseq6000による大規模シーケンスを実行した。
SHIROKANEパイプラインへの登録保存からgenomonによるcurationを完了し、TCGAを超える規模の世界最大級のオミックスデータ解析の準備が完了した。
約500例のうち、化学放射線療法210例、免疫チェックポイント阻害薬使用例70例となっており、多彩な臨床治療とその奏功の関係性を解析できる理想的なデータ構築が実現できている。
特定のMolecular subtypeとdriver gene alterationの相関を明らかにし、化学放射線療法症例でのexceptional responderに焦点を充てた解析を行っている。派生する研究プロジェクトの解析結果として、血中neutrophil-lymphocyte ratio (NLR)とtertially lymphoid structure (TLS)有無による免疫チェックポイント阻害薬奏功の関係性を解析した。解析可能検体であった100例のうちNLR中央値で2群に分けたところ、NLR低値の症例ではチェックポイント阻害薬奏功率が高いのに対し、NLR高値ではチェックポイント阻害薬の奏功率は0%であった。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

派生データを使用した発表論文を2報、Cancer Science, Molecular Cancerに報告しており、研究は順調に進捗している。

Strategy for Future Research Activity

Codexフェノサイクラーによるオリゴバーコードを使用した多重免疫染色システムを用いて、500例のtissue microarrayを40種類以上の多重免疫染色をおこなう免疫微小環境アトラスの作製を行う計画を準備している段階である。

Report

(3 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (16 results)

All 2023 2022 2021

All Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The Impact of FGFR3 Alterations on the Tumor Microenvironment and the Efficacy of Immune Checkpoint Inhibitors in Bladder Cancer2023

    • Author(s)
      Komura K, Hirosuna K, Tokushige S, Nishimura K, Ishida M, Hayashi T, Ura A, Ohno T, Yamazaki S, Nakamori K, Kinoshita S, Tsujino T, Maenosono R, Ajiro M, Yoshikawa Y, Takai T, Tsutsumi T, Taniguchi K, Tanaka T, Takahara K, Konuma T, Inamoto T, Hirose Y, Ono F, Shiraishi Y, Yoshimi A#, Azuma H.
    • Journal Title

      Molecular Cancer

      Volume: 22 Issue: 1 Pages: 185-185

    • DOI

      10.1186/s12943-023-01897-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antitumor effects of chemically modified miR-143 lipoplexes in a mouse model of pelvic colorectal cancer via myristoylated alanine-rich C kinase substrate downregulation2023

    • Author(s)
      Arima Jun、Taniguchi Kohei、Sugito Nobuhiko、Heishima Kazuki、Tokumaru Yoshihisa、Inomata Yosuke、Komura Kazumasa、Tanaka Tomohito、Shibata Masa-Aki、Lee Sang-Woong、Akao Yukihiro
    • Journal Title

      Molecular Therapy - Nucleic Acids

      Volume: 34 Pages: 102079-102079

    • DOI

      10.1016/j.omtn.2023.102079

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tertiary lymphoid structure and neutrophil?lymphocyte ratio coordinately predict outcome of pembrolizumab2023

    • Author(s)
      Komura K,Tokushige S, Ishida M, Hirosuna K,Yamazaki S,Nishimura K,Ajiro M,Ohno T,Nakamori K,Kinoshita S,Tsujino T, Maenosono R,Yoshikawa Y, Takai T, Tsutsumi T,Taniguchi K,Tanaka T,Takahara K, Inamoto T,Hirose Y, Ono F,Shiraishi Y,Yoshimi A,Azuma H.
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 12 Pages: 4622-31

    • DOI

      10.1111/cas.15976

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Concurrent palliative radiation with pembrolizumab for platinum-refractory urothelial carcinoma is associated with improved overall survival2022

    • Author(s)
      Nakamori K, Yamazaki S, Komura K, Fukuokaya W, Adachi T, Hirasawa Y, Hashimoto T, Yoshizawa A, Ohno T, Yano Y, Nishimura K, Tokushige S, Uchimoto T, Yamamoto S, Iwatani K, Urabe F, Mori K, Yanagisawa T, Tsuduki S, Takahara K, Inamoto T, Miki J, Kimura T, Ohno Y, Shiroki R, Azuma H.
    • Journal Title

      Clin Transl Radiat Oncol.

      Volume: 39 Pages: 5659-5659

    • DOI

      10.1016/j.ctro.2022.12.001

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum C-reactive Protein Level Predicts Overall Survival for Clear Cell and Non-Clear Cell Renal Cell Carcinoma Treated with Ipilimumab plus Nivolumab.2022

    • Author(s)
      Yano Y, Ohno T, Komura K, Fukuokaya W, Uchimoto T, Adachi T, Hirasawa Y, Hashimoto T, Yoshizawa A, Yamazaki S, Tokushige S, Nishimura K, Tsujino T, Nakamori K, Yamamoto S, Iwatani K, Urabe F, Mori K, Yanagisawa T, Tsuduki S, Takahara K, Inamoto T, Miki J, Kimura T, Ohno Y, Shiroki R, Azuma H.
    • Journal Title

      Cancers

      Volume: 14 Issue: 22 Pages: 5659-69

    • DOI

      10.3390/cancers14225659

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypoxia regulates tumour characteristic <scp>RNA</scp> modifications in ovarian cancers2022

    • Author(s)
      Monoe Yuya、Miyamoto Shunsuke、Jingushi Kentaro、Tanimoto Masaya、Tanaka Tomohito、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide、Tsujikawa Kazutake
    • Journal Title

      The FEBS Journal

      Volume: 290 Issue: 8 Pages: 2085-2096

    • DOI

      10.1111/febs.16688

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-Term Outcomes of Laparoscopic and Open Distal Pancreatectomy Using Propensity-Score Analysis: A Real-World Retrospective Cohort Study2022

    • Author(s)
      Ota Masato、Asakuma Mitsuhiro、Taniguchi Kohei、Ito Yuri、Komura Kazumasa、Tanaka Tomohito、Yamakawa Kazuma、Ogura Takeshi、Nishioka Daisuke、Hirokawa Fumitoshi、Uchiyama Kazuhisa、Lee Sang-Woong
    • Journal Title

      Annals of Surgery

      Volume: Publish Ahead of Print Issue: 4 Pages: e805-e811

    • DOI

      10.1097/sla.0000000000005758

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Re‐challenging chemotherapy after pembrolizumab in platinum‐refractory urothelial carcinoma2022

    • Author(s)
      Uchimoto Taizo、Fukushima Tatsuo、Komura Kazumasa、Fukuokaya Wataru、Adachi Takahiro、Mori Keiichiro、Yanagisawa Takafumi、Tsuduki Shunsuke、Takahara Kiyoshi、Inamoto Teruo、Miki Jun、Kimura Takahiro、Ohno Yoshio、Shiroki Ryoichi、Egawa Shin、Azuma Haruhito
    • Journal Title

      BJU International

      Volume: 131 Issue: 4 Pages: 477-85

    • DOI

      10.1111/bju.15893

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of the fluctuation in the neutrophil lymphocyte ratio at 6 weeks of pembrolizumab treatment is specific to the clinical response in metastatic urothelial carcinoma.2022

    • Author(s)
      Uchimoto T,Nakamura K, Komura K, Fukuokaya W, Yano Y, Nishimura K, Kinoshita S, Nishio K, Fukushima T, Nakamori K, Matsunaga T, Tsutsumi T, Tsujino T, Taniguchi K, Tanaka T, Uehara H, Takahara K, Inamoto T, Kimura T, Egawa S, Azuma H.
    • Journal Title

      Urologic oncology

      Volume: 40 Issue: 7 Pages: 11-17

    • DOI

      10.1016/j.urolonc.2022.02.012

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors2022

    • Author(s)
      Fukuokaya W,Kimura T,Komura K,Uchimoto T,Nishimura K,Yanagisawa T,Kosuke Y,Kagenori I,Fumihiko I,Shunsuke U,Shoji T,Naoki K,Shoichiro T,Mukai S,Oyamad Y,Abe H,Kamoto T,Azuma H,Miki J,Egawa S.
    • Journal Title

      Urologic Oncology: Seminars and Original Investigations

      Volume: 22 Issue: 7 Pages: 346.e1-346.e8

    • DOI

      10.1016/j.urolonc.2022.02.020

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy of pembrolizumab and comprehensive CD274/PD-L1 profiles in patients previously treated with chemoradiation therapy as radical treatment in bladder cancer2022

    • Author(s)
      Nishimura k, Nishio K, Hirosuna K,Komura K, Hayashi T,Fukuokaya W, Ura A,Uchimoto T, Nakamura K, Fukushima T,Yano Y,Takahashi N, Nakamori K, Kinoshita S,Matsunaga T, Tsutsumi T,Tsujino T,Taniguchi K,Tanaka T,Uehara H, Takahara K,Inamoto T,Hirose Y,Kimura T,Egawa S,Azuma H.
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 10 Issue: 1 Pages: e003868-e003868

    • DOI

      10.1136/jitc-2021-003868

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 高~超高リスク膀胱がんの根治を目指した未来の治療2023

    • Author(s)
      小村和正、辻野拓也、稲元輝生、東治人.
    • Organizer
      第61回日本癌治療学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] The Association of FGFR Genetic Alternation with CD274/PD-L1 Profi ling in Bladder Cancer2022

    • Author(s)
      Kazumasa Komura
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] FGFR muts/fusion-CD274/PD-L1のマルチオミクス解析~最適化医療応用の可能性~2022

    • Author(s)
      Kazumasa Komura
    • Organizer
      第60回日本癌治療学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Therapeutic Utility of ATM Inhibitor to Chemoradiation-Resistant Urothelial Carcinoma with Aberrant BUBR1 Expression.2021

    • Author(s)
      Kazumasa Komura.
    • Organizer
      第80回 日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 表在性膀胱がん浸潤性に関わる因子解明2023

    • Inventor(s)
      石田 光明
    • Industrial Property Rights Holder
      小村和正
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2024-12-25  

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