[EGFR and gefitinib (Iressa)]

Gan To Kagaku Ryoho. 2008 Jul;35(7):1076-9.
[Article in Japanese]

Abstract

We summarized the relationship between EGFR gene polymorphisms/mutations and gefitinib(Iressa). The SNPs of CA-simple sequence repeat of EGFR intron 1 and promoter sequence were reported to be related to the sensitivity and/ or toxicity of gefitinib(Iressa). Many reports have shown that there are differences between gefitinib responders and non-responders in the frequency of activating mutations and/or amplification in the EGFR gene, which suggests that such mutations might be predictive markers for sensitivity to gefitinib. However, there are known to be gefitinib-sensitive and intermediate-sensitive tumors that have no activating mutations in the EGFR gene, including gene amplification. SNPs in EGFR gene may be one of candidates for predictors of sensitivity. On the other hand, the incidence of gefitinib-induced lung injury was 3.98% in Japan(case-control study, AstraZeneca), which is higher than the correspondence rate, 0.3%, in the USA(FDA Approval Letter). Further studies about the prediction of drug-induced interstitial lung disease including SNPs analyses of the EGFR gene and other related molecules.

MeSH terms

  • Animals
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Gefitinib
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Polymorphism, Genetic / genetics
  • Promoter Regions, Genetic / genetics
  • Quinazolines / pharmacology*
  • Quinazolines / therapeutic use
  • Substrate Specificity

Substances

  • Quinazolines
  • ErbB Receptors
  • Gefitinib