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マルチオミクス解析による免疫チェックポイント阻害剤低感受性肺癌の効果予測因子同定

Research Project

Project/Area Number 22K07175
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionWakayama Medical University

Principal Investigator

赤松 弘朗  和歌山県立医科大学, 医学部, 准教授 (10646582)

Co-Investigator(Kenkyū-buntansha) 山本 信之  和歌山県立医科大学, 医学部, 教授 (60298966)
洪 泰浩  和歌山県立医科大学, 医学部, 准教授 (80426519)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords免疫チェックポイント阻害剤 / EGFR遺伝子変異 / 非小細胞肺がん
Outline of Research at the Start

我々が行ったEGFR Mtに対する化学療法+ICIの医師主導治験で回収した手術検体を用いて、マルチオミクス解析(次世代シーケンサーによる網羅的ゲノム解析・トランスクリプトーム解析・蛋白発現解析)を行い、ICI低感受性肺がんであるEGFR Mtにおける化学療法+ICIの効果予測因子を検討するとともに、不応例については耐性機序を同定し、これに基づく新規治療標的の探索を行う。

Outline of Annual Research Achievements

本体研究である完全切除、病理病期II-IIIA期のEGFR遺伝子変異陽性非小細胞肺がんに対するプラチナ併用療法+アテゾリズマブ術後補助化学療法の有効性および安全性を探索する多施設共同第II相試験(ADJUST試験、JapicCTI-194849)は解析を終了し、2024年9月の欧州臨床腫瘍学会、11月の日本肺癌学会総会にて結果を報告予定である(抄録投稿済み)。組織検体を用いた附随研究については倫理委員会にて承認を受け、全症例の組織検体を収集完了した。現在当科でDNA/RNAの抽出を完了し解析に進んでいる。DNA解析は終了しており、現在RNA解析も進行中である。

Current Status of Research Progress
Current Status of Research Progress

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

Reason

検体の集積、解析開始までは順調に推移している。今後、解析結果と臨床情報の突合を進めていく。

Strategy for Future Research Activity

DNAを用いた網羅的遺伝子変異解析の結果を元に、Tumor mutation burdenによる効果の違いや奏効・非奏効に関わる因子を同定を検討する。EGFR遺伝子変異陽性例では従来から免疫抑制性シグナルの亢進が言われており、RNAを用いた遺伝子発現解析によって効果予測因子の検討を進める。

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (10 results)

All 2024 2023 2022

All Journal Article (10 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results)

  • [Journal Article] PRMT5 is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer2024

    • Author(s)
      Lin Chang-Ching, Hiroaki Akamatsu, et al.
    • Journal Title

      Nature Communications

      Volume: 15 Issue: 1

    • DOI

      10.1038/s41467-024-46495-2

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mannitol versus furosemide in patients with thoracic malignancies who received cisplatin‐based chemotherapy using short hydration: A randomized phase <scp>II</scp> trial2024

    • Author(s)
      Murakami Eriko、Akamatsu Hiroaki、Teraoka Shunsuke、Takakura Toshiaki、Takase Eri、Tanaka Masanori、Kaki Takahiro、Harutani Yuhei、Furuta Katsuyuki、Sugimoto Takeya、Shibaki Ryota、Fujimoto Daichi、Hayata Atsushi、Ozawa Yuichi、Nakanishi Masanori、Koh Yasuhiro、Shimokawa Toshio、Yamamoto Nobuyuki
    • Journal Title

      Cancer Medicine

      Volume: 13 Issue: 4

    • DOI

      10.1002/cam4.6839

    • Related Report
      2023 Research-status Report
  • [Journal Article] Machine learning analysis of pathological images to predict 1-year progression-free survival of immunotherapy in patients with small-cell lung cancer2024

    • Author(s)
      Shibaki Ryota、Fujimoto Daichi、Nozawa Tsukasa、Sano Akira、Kitamura Yuka、Fukuoka Junya、Sato Yuki、Kijima Takashi、Matsumoto Hirotaka、Yokoyama Toshihide、Miura Satoru、Hata Akito、Tamiya Motohiro、Taniguchi Yoshihiko、Sugisaka Jun、Furuya Naoki、Tanaka Hisashi、Yamamoto Nobuyuki、Koh Yasuhiro、Akamatsu Hiroaki
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 12 Issue: 2 Pages: e007987-e007987

    • DOI

      10.1136/jitc-2023-007987

    • Related Report
      2023 Research-status Report
  • [Journal Article] Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL)2023

    • Author(s)
      Miura Satoru, Nishio Makoto, Akamatsu Hiroaki, et al.
    • Journal Title

      JTO Clinical and Research Reports

      Volume: 4 Issue: 3 Pages: 100484-100484

    • DOI

      10.1016/j.jtocrr.2023.100484

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biomarker Testing in Patients With Unresectable Advanced or Recurrent Non?Small Cell Lung Cancer2023

    • Author(s)
      Sakamoto Tomohiro, Hiroaki Akamatsu, et al.
    • Journal Title

      JAMA Network Open

      Volume: 6 Issue: 12 Pages: e2347700-e2347700

    • DOI

      10.1001/jamanetworkopen.2023.47700

    • Related Report
      2023 Research-status Report
  • [Journal Article] Carboplatin and irinotecan (CI) vs. carboplatin and etoposide (CE) for the treatment of extended-stage small-cell lung cancer in an elderly population: A phase II/III randomized control trial2023

    • Author(s)
      Shimokawa Tsuneo、Okamoto Hiroaki、Machida Ryunosuke、Misumi Yuki、Hosomi Yukio、Yoneshima Yasuto、Tanaka Hiroshi、Okishio Kyoichi、Simizu Junichi、Goto Koichi、Akamatsu Hiroaki、Kubota Kaoru、Nakagawa Kazuhiko、Horinouchi Hidehito、Ando Masahiko、Kataoka Tomoko、Ohe Yuichiro
    • Journal Title

      Lung Cancer

      Volume: 181 Pages: 107195-107195

    • DOI

      10.1016/j.lungcan.2023.107195

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Randomized, open-label phase II study of brigatinib and carboplatin plus pemetrexed and brigatinib alone for chemotherapy-naive patients with ALK-rearranged non-squamous non-small cell lung cancer: Treatment Rationale and Protocol Design of the B-DASH Study (WJOG 14720 L)2023

    • Author(s)
      Wakuda Kazushige、Kenmotsu Hirotsugu、Sato Yuki、Nakamura Atsushi、Akamatsu Hiroaki、Tachihara Motoko、Miura Satoru、Yokoyama Toshihide、Mori Keita、Nakagawa Kazuhiko、Yamamoto Nobuyuki
    • Journal Title

      BMC Cancer

      Volume: NA

    • DOI

      10.21203/rs.3.rs-2550375/v1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Outcomes of Chemoimmunotherapy Among Patients With Extensive-Stage Small Cell Lung Cancer According to Potential Clinical Trial Eligibility2023

    • Author(s)
      Fujimoto Daichi, Akamatsu Hiroaki, et al.
    • Journal Title

      JAMA Network Open

      Volume: 6 Issue: 2 Pages: e230698-e230698

    • DOI

      10.1001/jamanetworkopen.2023.0698

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential properties of KRAS transversion and transition mutations in non-small cell?lung cancer: associations with environmental factors and clinical outcomes2022

    • Author(s)
      Sato Koichi、Akamatsu Hiroaki、Koh Yasuhiro、Ogawa Koichi、Isa Shun-ichi、Ando Masahiko、Tamiya Akihiro、Kubo Akihito、Kitagawa Chiyoe、Kawaguchi Tomoya、Yamamoto Nobuyuki
    • Journal Title

      BMC Cancer

      Volume: 22 Issue: 1

    • DOI

      10.1186/s12885-022-10246-7

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nivolumab Retreatment in Non?Small Cell Lung Cancer Patients Who Responded to Prior Immune Checkpoint Inhibitors and Had ICI-Free Intervals (WJOG9616L)2022

    • Author(s)
      Akamatsu Hiroaki、Teraoka Shunsuke、Takamori Shinkichi、Miura Satoru、Hayashi Hidetoshi、Hata Akito、Toi Yukihiro、Shiraishi Yoshimasa、Mamesaya Nobuaki、Sato Yuki、Furuya Naoki、Oyanagi Jun、Koh Yasuhiro、Misumi Toshihiro、Yamamoto Nobuyuki、Nakagawa Kazuhiko
    • Journal Title

      Clinical Cancer Research

      Volume: 28 Issue: 15 Pages: 3207-3213

    • DOI

      10.1158/1078-0432.ccr-22-0602

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2022-04-19   Modified: 2024-12-25  

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