• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Research on Molecular Therapeutic Targets and Biomarkers for the Diagnosis and Stratification in Lung Cancer

Research Project

Project/Area Number 16390231
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHokkaido University

Principal Investigator

AKITA Hirotoshi  Hokkaido University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (70222528)

Co-Investigator(Kenkyū-buntansha) KINOSHITA Ichiro  Hokkaido University, Graduate SChool of Medicine, Lecturer, 大学院医学研究科, 講師 (40343008)
YAMAZAKI Koichi  Hokkaido University, Hokkaido University Hospital, Lecturer, 病院・講師 (20312358)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywordslung cancer / biomarker / AKR1B10 / EGFR mutation / 喫煙 / 扁平上皮癌 / タバコ発癌
Research Abstract

The aim of this research is to identify molecular therapeutic targets and Biomarkers for the diagnosis and stratification in lung cancer.
We searched for genes specifically overexpressed in lung cancer through microarray analysis, and identified seven genes, including AKRB1B10, in squamous cell carcinoma (SCC) of the lung. AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and in many adenocarcinomas from smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' non-small cell lung cancers (NSCLCs) and might be involved in tobacco-related carcinogenesis.
We next studied on the biomarker in molecular targeting therapy using EGF receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Retrospective analyses have shown that activating mutations in exons 18-21 of the EGFR gene are a predictor of response to EGFR-TKIs. We conducted a phase II study to evaluate the efficacy and safety of gefitinib, one of EGFR-TKIs, as first-line therapy for advanced NSCLCs with EGFR mutations. For mutation analysis, DNA was extracted from paraffin-embedded tissues and EGFR mutations were analysed by direct sequence of PCR products. Twenty (24%) of the 82 patients analysed had EGFR mutations. Sixteen patients were enrolled and treated with gefitinib. Twelve patients had objective response and response rate was 75%. This study has shown that mutations (deletions in exon 19 and L858R point mutation in exon 21) of the EGFR gene are a predictor of response to EGFR-TKIs.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (6 results)

All 2006 2005

All Journal Article (6 results)

  • [Journal Article] A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations2006

    • Author(s)
      Asahina H
    • Journal Title

      British Journal of Cancer 95・8

      Pages: 998-1004

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S7681 and V769L2006

    • Author(s)
      Asahina H
    • Journal Title

      Lung Cancer 54・3

      Pages: 419-422

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations.2006

    • Author(s)
      Asahina H, et al.
    • Journal Title

      British Journal of Cancer 95(8)

      Pages: 998-1004

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S768I and V769L.2006

    • Author(s)
      Asahina H, et al.
    • Journal Title

      Lung Cancer 54(3)

      Pages: 419-422

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas2005

    • Author(s)
      Fukumoto S
    • Journal Title

      Clinical Cancer Research 11・23

      Pages: 1776-1785

    • 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] Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers non-small cell lung carcinomas.2005

    • Author(s)
      Fukumoto S, et al.
    • Journal Title

      Clinical Cancer Research 11(23)

      Pages: 1776-1785

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi