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Understanding and overcoming drug resistance to EGFR-inhibitors for lung cancer

Research Project

Project/Area Number 25293302
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionOkayama University

Principal Investigator

Toyooka Shinichi  岡山大学, 医歯(薬)学総合研究科, 教授 (30397880)

Co-Investigator(Kenkyū-buntansha) SOH Junichi  岡山大学, 病院, 講師 (90559890)
MATSUDA Fumihiko  京都大学, 大学院医学研究科, 教授 (50212220)
YAMAMOTO Hiromasa  岡山大学, 病院, 助教 (40467733)
TSUKUDA Kazunori  岡山大学, 病院, 講師 (20346430)
ASANO Hiroaki  岡山大学, 病院, 助教 (70534775)
MIYOSHI Shinichiro  岡山大学, 大学院医歯薬学総合研究科, 教授 (00190827)
SHIEN Kazuhiko  岡山大学, 大学院医歯薬学総合研究科, 助教 (30708079)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords原発性肺癌 / 薬剤耐性 / 癌幹細胞 / 上皮成長因子受容体チロシンキナーゼ阻害剤 / 上皮間葉移行 / 上皮成長因子受容体チロシンキナーゼ阻害薬
Outline of Final Research Achievements

In this study, we aimed to understand and overcome drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) for lung cancer. We established EGFR-TKI resistant lung cancer cell lines, and specified several resistant mechanisms to EGFR-TKI by using these cell lines. Among them, we identified that acquiring of stem-cell like characteristics led to EGFR-TKI resistance, and several novel drugs were still effective to EGFR-TKI resistant cells. It is important to select an appropriate drug to treat acquired EGFR-TKI resistant cells according to each resistant mechanism.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (9 results)

All 2015 2014

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Acquisition of cancer stem cell-like properties in non-small cell lung cancer with acquired resistance to afatinib2015

    • Author(s)
      Shinsuke Hashida, Hiromasa Yamamoto, Kazuhiko Shien, Yuichiro Miyoshi, Tomoaki Ohtsuka, Ken Suzawa, Mototsugu Watanabe, Yuho Maki, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
    • Journal Title

      Cancer Science

      Volume: 10 Issue: 10 Pages: 1377-1384

    • DOI

      10.1111/cas.12749

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hsp90 inhibitor NVP-AUY922 enhances the radiation sensitivity of lung cancer cell lines with acquired resistance to EGFR-tyrosine kinase inhibitors.2015

    • Author(s)
      Hashida S, Yamamoto H, Shien K, Ohtsuka T, Suzawa K, Maki Y, Furukawa M, Soh J, Asano H, Tsukuda K, Miyoshi S, Kanazawa S, Toyooka S
    • Journal Title

      Oncology Reports

      Volume: 33 Issue: 3 Pages: 1499-1504

    • DOI

      10.3892/or.2015.3735

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TAE226, a Bis-Anilino Pyrimidine Compound, Inhibits the EGFR-Mutant Kinase Including T790M Mutant to Show Anti-Tumor Effect on EGFR-Mutant Non-Small Cell Lung Cancer Cells2015

    • Author(s)
      Otani H, Yamamoto H, Takaoka M, Sakaguchi M, Soh J, Jida M, Ueno T, Kubo T, Asano H, Tsukuda K, Kiura K, Hatakeyama S, Kawahara E, Naomoto Y, Miyoshi S, Toyooka S
    • Journal Title

      PLoS One

      Volume: 10 Issue: 6 Pages: e0129838-e0129838

    • DOI

      10.1371/journal.pone.0129838

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Docetaxel-resitant non-small cell lung cancer cells that acquired cross-resistance to EGFR-tyrosine kinase inhibitor2015

    • Author(s)
      Haiyang Chen, Ken Suzawa, Shinsuke Hashida, Tomoaki Ohtsuka, Mototsugu Watanabe, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Anti-tumor effect of a bis-anilino pyrimidine compound TAE226 on EGFR-mutant non-small cell lung cancer cells with or without T790M mutation2015

    • Author(s)
      Hiromasa Yamamoto, Hiroki Otani, Munenori Takaoka, Masakiyo Sakaguchi, Junichi Soh, Masaru Jida, Tsuyoshi Ueno, Takafumi Kubo, Hiroaki Asano, Kazunori Tsukuda, Katsuyuki Kiura, Shinji Hatakeyama, Eiji Kawahara, Yoshio Naomoto, Shinichiro Miyoshi, Shinichi Toyooka
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] TAE226, a bis-anilino pyrimidine compound, shows anti-tumor effect on EGFR-mutant non-small cell lung cancer cells including T790M mutant2015

    • Author(s)
      Hiromasa Yamamoto, Hiroki Otani, Munenori Takaoka, Masakiyo Sakaguchi, Junichi Soh, Masaru Jida, Tsuyoshi Ueno, Takafumi Kubo, Hiroaki Asano, Kazunori Tsukuda, Katsuyuki Kiura, Shinji Hatakeyama, Eiji Kawahara, Yoshio Naomoto, Shinichiro Miyoshi, Shinichi Toyooka
    • Organizer
      16th World Conference on Lung Cancer
    • Place of Presentation
      米国
    • Year and Date
      2015-09-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of Hsp90 inhibitor NVP-AUY922 with radiation on lung adenocarcinoma cell lines with acquired resistance to EGFR-tyrosine kinase inhibitors2015

    • Author(s)
      Yuho Maki, Shinsuke Hashida, Hiromasa Yamamoto, Kazuhiko Shien, Tomoaki Ohtsuka, Ken Suzawa, Masashi Furukawa, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Susumu Kanazawa, Shinichi Toyooka
    • Organizer
      AACR 106th Annual Meeting
    • Place of Presentation
      米国
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The molecular characters of acquired resistant non-small cell lung cancer cells to afatinib2014

    • Author(s)
      Shinsuke Hashida, Shinichi Toyooka, Tomoaki Ohtsuka, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyosh
    • Organizer
      AACR Annual Meeting 2014
    • Place of Presentation
      San Diego, California, U.S.A
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] The molecular characters of acquired resistant non-small cell lung cancer cells to afatinib2014

    • Author(s)
      Shinsuke Hashida, Shinichi Toyooka, Tomoaki Ohtsuka, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda,Shinichiro Miyoshi
    • Organizer
      AACR Annual Meeting 2014
    • Place of Presentation
      San Diego, California, U.S.A
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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