Cancer Chemotherapy and Pharmacology

, Volume 58, Supplement 1, pp 25–31

The impact and role of EGFR gene mutation on non-small cell lung cancer

  • Shinichi Toyooka
  • Junichi Soh
  • Hisayuki Shigematsu
  • Motoi Aoe
  • Hiroshi Date
Article

DOI: 10.1007/s00280-006-0312-8

Cite this article as:
Toyooka, S., Soh, J., Shigematsu, H. et al. Cancer Chemother Pharmacol (2006) 58(Suppl 1): 25. doi:10.1007/s00280-006-0312-8

Abstract

Mutations in the epidermal growth factor receptor (EGFR) gene have been reported in non-small cell lung cancer (NSCLC), especially in patients with adenocarcinomas, women, never smokers, and East Asians. These factors were recognized as predictors of gefitinib response in the Iressa Dose Evaluation in Advanced Lung Cancer study. Despite some contradictory arguments, somatic mutations in EGFR have been demonstrated to be a useful biomarker for predicting the clinical outcome of treatment with gefitinib or erlotinib, indicating the necessity of validated assays for clinical applications. Mutations in EGFR and KRAS are established carcinogenic mechanisms responsible for NSCLC. Recent studies have demonstrated that epigenetic alteration is another critical mechanism in lung carcinogenesis. Notably, EGFR and KRAS mutations are mutually exclusive, suggesting the presence of two independent pathways for the development of adenocarcinoma; however, the relationship between mutation and epigenetic alteration is not known. To address these issues, we examined the EGFR mutation status in Japanese patients with NSCLC by direct sequencing exons 18–21 of EGFR; the results were then correlated with clinicopathological factors and previously investigated epigenetic alterations. In this article, we mainly focus on: (1) the relationship between EGFR mutations and clinicopathological factors, (2) the relationship between EGFR mutations and response to gefitinib, (3) the development of a sensitive assay for detecting the major EGFR mutations, and (4) differences in the evolution of epigenetic alterations between EGFR- or KRAS-mediated tumorigenesis. The present results provide important data for translational research and will further our understanding of the molecular pathogenesis of NSCLC, leading to the establishment of molecular targeting strategies for the treatment of NSCLC.

Keywords

EGFR KRAS NSCLC Methylation Gefitinib Erlotinib 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Shinichi Toyooka
    • 1
  • Junichi Soh
    • 1
  • Hisayuki Shigematsu
    • 1
  • Motoi Aoe
    • 1
  • Hiroshi Date
    • 1
  1. 1.Department of Cancer and Thoracic Surgery, Graduate School of Medicine and DentistryOkayama UniversityOkayamaJapan

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