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Novel therapeutic strategy focused on EGFR-binding protein LRIG1 for EGFR-mutant lung cancer

Research Project

Project/Area Number 18K08783
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionOkayama University

Principal Investigator

Yamamoto Hiromasa  岡山大学, 大学病院, 助教 (40467733)

Co-Investigator(Kenkyū-buntansha) 冨田 秀太  岡山大学, 大学病院, 准教授 (10372111)
豊岡 伸一  岡山大学, 医歯薬学総合研究科, 教授 (30397880)
枝園 和彦  岡山大学, 大学病院, 助教 (30708079)
宗 淳一  近畿大学, 医学部, 准教授 (90559890)
諏澤 憲  岡山大学, 大学病院, 助教 (90839713)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords肺癌 / EGFR / LRIG1 / EGFR遺伝子変異
Outline of Final Research Achievements

This study was to establish the novel therapeutic strategy focused on EGFR-binding protein LRIG1, by evaluating the anti-tumor effect of LRIG1 to EGFR-mutant lung cancer. We established EGFR-mutant and EGFR-wild type lung cancer cell lines that stably expressed LRIG1. Using these cell lines, we evaluated EGFR expression status and cell growth in vitro and in vivo. LRIG1 inhibited the expression of mutant EGFR and its phosphorylation, and cell growth in EGFR-mutant lung cancer cell lines. On the other hand, LRIG1 did not affect EGFR expression or cell growth in EGFR-wild type lung cancer cell lines.

Academic Significance and Societal Importance of the Research Achievements

EGFR変異陽性肺癌に対して、EGFRチロシンキナーゼ阻害剤は劇的な治療効果を示すが、奏効した症例も大部分が約1年で耐性を獲得し再発する。獲得耐性因子としてはEGFRのT790M二次的遺伝子変異やMET 遺伝子増幅などが国内外から報告されており、その耐性の克服や、異なる機序で抗腫瘍効果を発揮する新規薬剤の開発が期待されている。EGFR変異陽性肺癌に対するLRIG1の抗腫瘍効果が実験的に証明されたため、LRIG1は治療薬剤となり得ることが示された。肺癌は日本において最も死亡者数の多い癌であり、肺癌の治療成績の向上は社会的にも意義が大きいと考えられる。

Report

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

    (2 results)

All 2018

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

  • [Journal Article] Tumor-suppressive effect of LRIG1, a negative regulator of ErbB, in non-small cell lung cancer harboring mutant EGFR2018

    • Author(s)
      Torigoe H, Yamamoto H, Sakaguchi M, Youyi C, Numba K, Sato H, Shien K, Soh J, Suzawa K, Tomida S, Tsukuda K, Miyoshi S, Toyooka S
    • Journal Title

      Carcinogenesis

      Volume: - Issue: 5 Pages: 719-727

    • DOI

      10.1093/carcin/bgy044

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] EGFR 変異陽性肺癌における LRIG1 の抗腫瘍効果2018

    • Author(s)
      鳥越 英次郎、山本 寛斉、阪口 政清、難波 圭、佐藤 博紀、枝 園 和彦、諏澤 憲、宗 淳一、冨田 秀太、佃 和憲、三好 新一郎、 豊岡 伸一
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report

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

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