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Investigation of the relationship between EGFR gene status and clinical effect and the elucidation of the resistance mechanism

Research Project

Project/Area Number 17590812
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNHO Kinki-Chuo Chest Medical Center Clinical Research Center

Principal Investigator

TAKADA Minoru  NHO Kinki-Chuo Chest Medical Center Clinical Research Center, Thoracic Oncology, Director, 肺がん研究部, 部長 (20373516)

Co-Investigator(Kenkyū-buntansha) OKADA Masaji  NHO Kinki-Chuo Chest Medical Center Clinical Research Center, Chief Director, 臨床研究センター, 臨床研究センター長 (40160684)
KAWAHARA Masaoki  NHO Kinki-Chuo Chest Medical Center, Chief Professional Service, 統括診療部, 部長 (30344352)
SASAKI Hidefumi  Nagoya City University, Medical School. Surgery II, Assistant Professor, 大学院医学研究科病態外科学腫瘍・免疫外科学, 助教 (00336695)
FUKUOKA Jyunya  Toyama university hospital, Laboratory of Pathology, Assistant Professor, 附属病院病理部, 准教授 (00324575)
OKAMOTO Isamu  Kinki University, School of Medicine. Medical Oncology, Assistant Professor, 医学部腫瘍内科, 講師 (10411597)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsNon Small Cell Lung Cancer / Epidermal Growth Factor / tyrosine kinase inhibitor / somatic mutation / gene amplification / auto-phosphorylation / dimerization / チロシンキナーゼ阻害剤(TKIs) / 非小細胞肺癌 / EGFR / EGFR-TKIs / Gefitinib / ミスセンス変異 / インフレーム変異 / コピー数の増加 / KRAS
Research Abstract

In this study, we investigate an effect and/or the resistance mechanism of the EGFR tyrosine kinase inhibitor (TKIs) in the non small-cell lung cancer (NSCLC) using clinical specimens which have the somatic mutation in the epidermal growth factor receptor (EGFR) gene tyrosine kinase domain, and the final aim is that we find a new biological marker. By the last year, we have performed retrospective analysis about an EGFR mutation and its correlation with the clinical response using the surgical specimen of our institution.
To investigate the influence of EGFR mutation and gene amplification to cancer growth and effects of EGFR-TKIs, we have examined 16 NSCLC cell lines, including eight newly established lines from Japanese NSCLC patients. Four of the six cell lines that harbor EGFR mutations were found to be positive for EGFR amplification (delE746-A750:2lines, L858R:2lines), whereas none of the 10 cell lines negative for EGFR mutation manifested EGFR amplification, suggesting that these two types of EGFR alteration are closely associated. Endogenous EGFRs expressed in NSCLC cell lines positive for both EGFR mutation and amplification were found to be constitutively activated as a result of ligand-independent dimerization. Furthermore, the patterns of both EGFR amplification and EGFR autophosphorylation were shown to differ between cell lines harboring the two most common types of EGFR mutation (exon-19 deletion and L858R point mutation in exon 21).
These results reveal distinct biochemical properties of endogenous mutant forms of the EGFR expressed in NSCLC cell lines and may have implications for treatment of this condition.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (8 results)

All 2007 2006 2005

All Journal Article (8 results)

  • [Journal Article] Differential constitutive activation of the Epidermal Growth Factor Receptor (EGFR) in non-small cell lung cancer cells bearing EGFR gene mutation and amplification.2007

    • Author(s)
      Isamu Okamoto
    • Journal Title

      Cancer Research. 67

      Pages: 2046-2053

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differential constitutive activation of the Epidermal Growth Factor Receptor (EGFR) in non-small cell lung cancer cells bearing EGFR gene mutation and amplification.2007

    • Author(s)
      Okabe T, Okamoto I, Tamura K, Terashima M, Yoshida T, Satoh T, Takada M, Fukuoka M, Nakagawa K
    • Journal Title

      Cancer Res 67(5)

      Pages: 2046-2053

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differential constitutive activation of the Epidermal Growth Factor Receptor (EGFR) in non- small cell lung cancer cells bearing EGFR gene mutation and amplification.2007

    • Author(s)
      Isamu Okamoto
    • Journal Title

      Cancer Research. 67

      Pages: 2046-2053

    • Related Report
      2006 Annual Research Report
  • [Journal Article] EGFR and erbB2 mutation status in Japanese lung cancer patients.2006

    • Author(s)
      Sasaki H
    • Journal Title

      Int J Cancer. 118(1)

      Pages: 180-184

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay.2005

    • Author(s)
      Endo K
    • Journal Title

      Lung Cancer. 50(3)

      Pages: 375-384

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] EGFR Mutation Status in Japanese Lung Cancer Patients : Genotyping Analysis Using LightCycler2005

    • Author(s)
      Sasaki H
    • Journal Title

      Clin Cancer Res 11(8)

      Pages: 2924-2929

    • NAID

      110007409623

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] EGFR変異とゲフィチニブの臨床効果が相関しなかった1例2005

    • Author(s)
      高田 實
    • Journal Title

      分子呼吸器病 Vol. 9 No. 4

      Pages: 58-62

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] EGFR変異とゲフィチニブの臨床効果が相関しなかった1例2005

    • Author(s)
      高田 實
    • Journal Title

      分子呼吸器病 Vol.9 No.4

      Pages: 58-62

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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