title: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-targeted therapy for advanced non-small cell lung cancer: molecular and clinical aspects.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. chi-okamoto@dotd.med.kindai.ac.jp
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D000077547:Crizotinib; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C415585:EML4 protein, human; D012697:Serine Endopeptidases