Drug resistance to EGFR tyrosine kinase inhibitors for non-small cell lung cancer

Kazuhiko Shiena, Hiromasa Yamamoto, Junichi Sou, Shinichiro Miyoshi, Shinichi Toyooka

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Non-small cell lung cancer (NSCLC) harboring an activating mutation within the epidermal growth factor receptor (EGFR) was defined as a clinically distinct molecular group. These lesions show oncogene addiction to EGFR and dramatic responses to the EGFR tyrosine kinase inhibitors (TKIs). Several large Phase III trials have shown that EGFR-TKIs improved the progression-free survival of patients with EGFR mutant NSCLC compared to conventional chemotherapy. However, the long-term effectiveness of EGFR-TKIs is usually limited because of acquired drug resistance. To overcome this resistance to EGFR-TKIs, it will be essential to identify the specific mechanisms underlying the resistance. Many investigators have attempted to identify the mechanisms using preclinical models and drug-resistant clinical samples. As a result, several mechanisms have been showed to be responsible for the resistance, but not all of the relevant mechanisms have been uncovered. In this review, we provide an overview of mechanisms underlying drug-resistance to EGFR-TKIs, focusing on results obtained with preclinical models, and we present some possible strategies to overcome the EGFR-TKI resistance.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalActa Medica Okayama
Volume68
Issue number4
Publication statusPublished - 2014

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Keywords

  • Cancer stem cell
  • Drug resistance
  • EGFR mutation
  • Non-small cell lung cancer
  • Tyrosine-kinase inhibitor

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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