Acquired resistance of non-small cell lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors

Fariz Nurwidya, Fumiyuki Takahashi, Akiko Murakami, Isao Kobayashi, Motoyasu Kato, Takehito Shukuya, Ken Tajima, Naoko Shimada, Kazuhisa Takahashi

Research output: Contribution to journalReview articlepeer-review

31 Citations (Scopus)

Abstract

Activation of epidermal growth factor receptor (EGFR) triggers anti-apoptotic signaling, proliferation, angiogenesis, invasion, metastasis, and drug resistance, which leads to development and progression of human epithelial cancers, including non-small cell lung cancer (NSCLC). Inhibition of EGFR by tyrosine kinase inhibitors such as gefitinib and erlotinib has provided a new hope for the cure of NSCLC patients. However, acquired resistance to gefitinib and erlotinib via EGFR-mutant NSCLC has occurred through various molecular mechanisms such as T790M secondary mutation, MET amplification, hepatocyte growth factor (HGF) overexpression, PTEN downregulation, epithelial-mesenchymal transition (EMT), and other mechanisms. This review will discuss the biology of receptor tyrosine kinase inhibition and focus on the molecular mechanisms of acquired resistance to tyrosine kinase inhibitors of EGFR-mutant NSCLC.

Original languageEnglish
Pages (from-to)82-91
Number of pages10
JournalRespiratory Investigation
Volume52
Issue number2
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Acquired resistance
  • Epidermal growth factor receptor (EGFR)
  • Non-small cell lung cancer (NSCLC)
  • Tyrosine kinase inhibitors

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