Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-targeted therapy for advanced non-small cell lung cancer: molecular and clinical aspects

Cancer Sci. 2012 Aug;103(8):1391-6. doi: 10.1111/j.1349-7006.2012.02327.x. Epub 2012 Jun 17.


The identification of oncogenic genomic alterations is expected to facilitate the development of new molecularly targeted therapies for cancer. EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) was recently identified as a transforming fusion gene in non-small cell lung cancer (NSCLC). A small-molecule tyrosine kinase inhibitor of ALK, crizotinib, shows pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK, and it has rapidly entered into daily clinical practice. This review focuses on the biology and clinical features of, as well as diagnostic testing for, EML4-ALK-positive NSCLC. Current data on the efficacy and toxicity of crizotinib are also examined, and future directions for the treatment of NSCLC positive for ALK rearrangement are addressed.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cell Cycle Proteins / genetics*
  • Crizotinib
  • Gene Expression Regulation, Neoplastic
  • Gene Fusion
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Microtubule-Associated Proteins / genetics*
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Serine Endopeptidases / genetics*
  • Signal Transduction


  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • EML4 protein, human
  • Serine Endopeptidases