Activity of EGFR-tyrosine kinase and ALK inhibitors for EML4-ALK-rearranged non-small-cell lung cancer harbored coexisting EGFR mutation

BMC Cancer. 2013 May 29:13:262. doi: 10.1186/1471-2407-13-262.

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.

Case presentation: 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.

Publication types

  • Case Reports

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Female
  • Genes, erbB-1
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Oncogene Proteins, Fusion / genetics
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors

Substances

  • EML4-ALK fusion protein, human
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases