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A study of molecular biology and liquid biopsy for non-small cell lung cancer positive for HER2 mutations

Research Project

Project/Area Number 18K15214
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKyushu University

Principal Investigator

Iwama Eiji  九州大学, 大学病院, 助教 (40567343)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsHER2 / 抗体薬物複合体 / リキッドバイオプシー / HER2遺伝子変異 / ダイマー / 分子標的治療薬 / 遺伝子変異 / ダイマー形成
Outline of Final Research Achievements

Trastuzumab emtansine, antibody-drug conjugate, was effective for EGFR mutated-cancer cell lines even though the expression of HER2 was low in the cell lines. Homodimer of HER2-HER2 was localized at the cell surface and heterodimers of HER2-EGFR or HER2-HER3 were located within cells, indicating that HER2 was internalized into cytoplasm via HER2-EGFR heterodimer in EGFR-mutated cell lines. Presence or increase or disappearance of the EGFR activating mutations in plasma was prognostic factors for EGFR-TKI treatment.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、HER2を標的とした分子標的治療薬がHER2高発現の腫瘍以外にも効果を有することが明らかとなり、更なる研究によって治療選択肢の拡大につながる可能性がある。現在、新規研究として「EGFR遺伝子変異陽性肺癌における抗体薬物複合体の作用機序に関する研究」を推進中である。2021年3月ゲノム医療の一環として次世代シークエンサーを用いたリキッドバイオプシー検査が承認され、今後リキッドバイオプシーが日常臨床で使用されるようになる。このような背景において、本研究で示した分子標的治療薬の予後予測におけるリキッドバイオプシーの有用性は重要な意義を有する。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Longitudinal monitoring of somatic genetic alterations in circulating cell-free DNA during treatment with epidermal growth factor receptor-tyrosine kinase inhibitors.2020

    • Author(s)
      Iwama E, Sakai K, Hidaka N, Inoue K, Fujii A, Nakagaki N, Ota K, Toyozawa R, Azuma K, Nakatomi K, Harada T, Hisasue J, Sakata S, Shimose T, Kishimoto J, Nakanishi Y, Nishio K, Okamoto I.
    • Journal Title

      Cancer

      Volume: 126(1) Issue: 1 Pages: 219-227

    • DOI

      10.1002/cncr.32481

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heregulin expression and its clinical implication for patients with EGFR-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors.2019

    • Author(s)
      Yonesaka K, Iwama E, Hayashi H, Suzuki S, Kato R, Watanabe S, Takahama T, Tanizaki J, Tanaka K, Takeda M, Sakai K, Azuma K, Chiba Y, Atagi S, Nishio K, Okamoto I, Nakagawa K.
    • Journal Title

      Scientific reports

      Volume: 9(1) Issue: 1 Pages: 19501-19501

    • DOI

      10.1038/s41598-019-55939-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic Profiling of Non‐Small Cell Lung Cancer at Development of Resistance to First‐ or Second‐Generation EGFR‐TKIs by CAPP‐Seq Analysis of Circulating Tumor DNA2019

    • Author(s)
      Otsubo Kohei、Sakai Kazuko、Takeshita Masafumi、Harada Daijiro、Azuma Koichi、Ota Keiichi、Akamatsu Hiroaki、Goto Koichi、Horiike Atsushi、Kurata Takayasu、Nakagaki Noriaki、Nosaki Kaname、Iwama Eiji、Nakanishi Yoichi、Nishio Kazuto、Okamoto Isamu
    • Journal Title

      The Oncologist

      Volume: 24 Issue: 8 Pages: 1022-1026

    • DOI

      10.1634/theoncologist.2019-0101

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploration of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain reaction and next-generation sequencing.2018

    • Author(s)
      Iwama E, Sakai K, Azuma K, Harada D, Nosaki K, Hotta K, Nishio M, Kurata T, Fukuhara T, Akamatsu H, Goto K, Shimose T, Kishimoto J, Nakanishi Y, Nishio K, Okamoto I.
    • Journal Title

      Cancer Sci

      Volume: 109 Issue: 12 Pages: 3921-3933

    • DOI

      10.1111/cas.13820

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] EGFR遺伝子変異陽性肺癌治療における大規模前向きリキッドバイオプシー研究2019

    • Author(s)
      岩間映二
    • Organizer
      第116 回日本内科学会講演会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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