title: Recent understanding of the molecular mechanisms for the efficacy and resistance of EGF receptor-specific tyrosine kinase inhibitors in non-small cell lung cancer.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) and its family members are involved in many aspects of tumor biological processes. Aberrant activation of the EGFR tyrosine kinase by mutations or protein overexpression is observed in various types of human cancer, including lung cancer. EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are highly effective in lung cancer patients who harbor active mutations in the EGFR gene. However, patients who are initially sensitive to EGFR-TKIs eventually relapse within few years.
  
  
  METHODS
  Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and is associated with a high frequency of EGFR mutations. This review describes the EGFR mutations that determine the sensitivity to EGFR-TKIs and the current understanding of the molecular mechanisms of acquired resistance to EGFR-TKIs in NSCLC. Furthermore, the authors describe recent strategies developed to overcome acquired resistance using second-generation EGFR-TKIs and combination therapies with several molecular-targeting drugs.
  
  
  CONCLUSIONS
  Although recent findings have contributed to our understanding of the mechanism of acquired resistance and helped the development of novel strategies to overcome such resistance, the underlying mechanisms are complex and additional research is necessary to develop effective therapeutic strategies for individual patients with lung cancer.
authors: University of Tokyo, Institute of Medical Science, Division of Systems Biomedical Technology, 4-6-1 Shirokanedai, Minatoku, Tokyo, 108-8639, Japan.
authors: Asuka
authors: A
authors: Nakata
authors: Noriko
authors: N
authors: Gotoh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors