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

Shinichi Toyooka, Junichi Soh, Hisayuki Shigematsu, Motoi Aoe, Hiroshi Date

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)s25-s31
JournalCancer Chemotherapy and Pharmacology
Volume58
Issue numberSUPPL.
DOIs
Publication statusPublished - Nov 2006

Keywords

  • EGFR
  • Erlotinib
  • Gefitinib
  • KRAS
  • Methylation
  • NSCLC

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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