title: Afatinib is especially effective against non-small cell lung cancer carrying an EGFR exon 19 deletion.
abstract: BACKGROUND
  A recent pooled analysis of the LUX-LUNG3 and LUX-LUNG6 trials suggested that afatinib (an irreversible epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)) is especially effective against non-small cell lung cancer (NSCLC) carrying an EGFR exon 19 deletion.
  
  
  METHODS
  Stable viral transfectant HEK293 cell lines carrying an exon 19 deletion (HEK293/19 del) or exon 21 L858R mutation (HEK293/ L858R)) were created and their drug sensitivities to AG1478 (a reversible EGFR-TKI) and afatinib were examined using an MTT assay. Western blot analyses were performed to estimate the phosphorylation of EGFR.
  
  
  RESULTS
  In the HEK293/19 del, the 50% inhibitory concentration (IC50) of afatinib was significantly lower than that in the HEK293/ L858R. In addition, afatinib inhibited the phosphorylation of EGFR to a greater degree in the HEK293/19 del than in the HEK293/L858R.
  
  
  CONCLUSIONS
  Our experimental findings suggest that afatinib is especially effective against NSCLC carrying an EGFR exon 19 deletion.
authors: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka, Japan.
authors: Eri
authors: E
authors: Banno
authors: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka, Japan.
authors: Yosuke
authors: Y
authors: Togashi
authors: Department of Surgery, Kinki University Faculty of Medicine, Osaka, Japan.
authors: Yoshihisa
authors: Y
authors: Kobayashi
authors: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka, Japan Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan Department of Medical Oncology, Kishiwada Municipal Hospital, Osaka, Japan.
authors: Hidetoshi
authors: H
authors: Hayashi
authors: Department of Surgery, Kinki University Faculty of Medicine, Osaka, Japan.
authors: Tetsuya
authors: T
authors: Mitsudomi
authors: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka, Japan knishio@med.kindai.ac.jp.
authors: Kazuto
authors: K
authors: Nishio
mesh_terms: D000077716:Afatinib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage*; D017384:Sequence Deletion
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Non-small cell lung cancer; afatinib; epidermal growth factor receptor gene mutation; exon 19 deletion; exon 21 L858R