title: Activity of EGFR-tyrosine kinase and ALK inhibitors for EML4-ALK-rearranged non-small-cell lung cancer harbored coexisting EGFR mutation.
abstract: BACKGROUND
  The EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLCs). The EML4-ALK fusion gene occurs generally in NSCLC without mutations in epidermal growth factor receptor (EGFR) and KRAS.
  
  
  METHODS
  We report that a case of EML4-ALK-positive NSCLC with EGFR mutation had a response of stable disease to both an EGFR tyrosine kinase inhibitor (EGFR-TKI) and ALK inhibitor.
  
  
  CONCLUSIONS
  We described the first clinical report of a patient with EML4-ALK-positive NSCLC with EGFR mutation that had a response of stable disease to both single-agent EGFR-TKI and ALK inhibitor. EML4-ALK translocation may be associated with resistance to EGFR-TKI, and EGFR signaling may contribute to resistance to ALK inhibitor in EML4-ALK-positive NSCLC.
authors.affiliation: Department of Pulmonary Medicine and Oncology, Nippon Medical School, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Miyanaga
authors.forename: Kumi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Rintaro
authors.initials: R
authors.lastname: Noro
authors.forename: Masahiro
authors.initials: M
authors.lastname: Seike
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kitamura
authors.forename: Seiji
authors.initials: S
authors.lastname: Kosaihira
authors.forename: Yuji
authors.initials: Y
authors.lastname: Minegishi
authors.forename: Takehito
authors.initials: T
authors.lastname: Shukuya
authors.forename: Akinobu
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Manabu
authors.initials: M
authors.lastname: Soda
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases