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EGFR mutant lung cancer and second generation tyrosine kinase inhibitor: acquired resistance and personalized medicine

Research Project

Project/Area Number 16K19989
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Respiratory surgery
Research InstitutionKindai University

Principal Investigator

KOBAYASHI Yoshihisa  近畿大学, 医学部附属病院, 助教 (30734628)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺癌 / EGFR / チロシンキナーゼ阻害剤 / アファチニブ / ダコミチニブ / L792F / 薬剤耐性 / 分子標的治療 / 耐性機序
Outline of Final Research Achievements

Targeted therapy with tyrosine kinase inhibitors (TKIs) is a standard treatment for patients with epidermal growth factor receptor (EGFR) mutant lung cancer. However, not all EGFR mutations are sensitive to conventional EGFR-TKIs. Additionally, lung cancers inevitably acquire resistance to these TKIs despite the marked initial response.
We found that lung cancers harboring exon 18 mutations were not sensitive to conventional first generation EGFR-TKIs but are sensitive to second generation TKI afatinib. Next, a novel EGFR L792F secondary mutation, in addition to T790M and C797S, was discovered in afatinib-resistant cells. L792F appeared to exhibit sensitivity to other second generation TKI dacomitinib. Dacomitinib induced T790M or C797S secondary mutations as mechanisms of acquired resistance and these mutations were sensitive to currently available TKIs.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] EGFR T790M and C797S Mutations as Mechanisms of Acquired Resistance to Dacomitinib2018

    • Author(s)
      Kobayashi Y, Fujino T, Nishino M, Koga T, Chiba M, Sesumi Y, Ohara S, Shimoji M, Tomizawa K, Takemoto T, Mitsudomi T
    • Journal Title

      Journal of Thoracic Oncology

      Volume: ePub中 Issue: 5 Pages: 727-731

    • DOI

      10.1016/j.jtho.2018.01.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ALK遺伝子転座陽性例への薬物療法-治療開始からラストラインまで2017

    • Author(s)
      小林祥久、光冨徹哉
    • Journal Title

      臨床腫瘍プラクティス

      Volume: 13 Pages: 16-20

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Characterization of EGFR T790M, L792F, and C797S Mutations as Mechanisms of Acquired Resistance to Afatinib in Lung Cancer2017

    • Author(s)
      Kobayashi, Y. Azuma, K. Nagai, H. Kim, Y. H. Togashi, Y. Sesumi, Y. Chiba, M. Shimoji, M. Sato, K. Tomizawa, K. Takemoto, T. Nishio, K. Mitsudomi, T.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 16 Pages: 357-364

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy2016

    • Author(s)
      Kobayashi, Y. Mitsudomi, T.
    • Journal Title

      Cancer Science

      Volume: 107 Issue: 9 Pages: 1179-1186

    • DOI

      10.1111/cas.12996

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Mechanisms of acquired resistance to dacomitinib in cell models2017

    • Author(s)
      Kobayashi Y, Fujino T, Nishino M, Ohara S, Sesumi Y, Chiba M, Shimoji M, Tomizawa K, Takemoto T, Mitsudomi T
    • Organizer
      World Conference on Lung Cancer
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular targeted therapy for EGFR mutant lung cancer: mutation-specific drug selection.2017

    • Author(s)
      Kobayashi Y
    • Organizer
      The Satelite Symposium of Biological Session of Japan Nucleic Acid Therapeutics
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アファチニブ獲得耐性機序としてのEGFR二次変異T790M、L792F、C797Sの特徴2016

    • Author(s)
      小林祥久、東公一、永井宏樹、金永学、冨樫庸介、瀬角裕一、西野将矢、西平守道、佐藤克明、千葉眞人、下治正樹、富沢健二、武本智樹、西尾和人、光冨徹哉
    • Organizer
      第57回日本肺癌学会学術集会
    • Place of Presentation
      福岡国際会議場 (福岡市)
    • Year and Date
      2016-12-20
    • Related Report
      2016 Research-status Report
  • [Presentation] EGFR T790M, L792F, and C797S mutations as mechanisms of acquired resistance to afatinib2016

    • Author(s)
      Kobayashi, Y. Azuma, K. Nagai, H. Kim, Y. H. Togashi, Y. Sesumi, Y. Chiba, M. Shimoji, M. Sato, K. Tomizawa, K. Takemoto, T. Nishio, K. Mitsudomi, T.
    • Organizer
      17th World Conference on Lung Cancer
    • Place of Presentation
      ウィーン (オーストリア)
    • Year and Date
      2016-12-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] 肺癌診療Q&A 第3版 一つ上を行く診療の実践 (分担執筆 P42-46, P326-329)2017

    • Author(s)
      小林祥久、光冨徹哉
    • Total Pages
      521
    • Publisher
      中外医学社
    • ISBN
      9784498131002
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-01-20  

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