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.
© 2012 Japanese Cancer Association.
MeSH terms
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Anaplastic Lymphoma Kinase
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Apoptosis
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / genetics
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Cell Cycle Proteins / genetics*
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Crizotinib
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Gene Expression Regulation, Neoplastic
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Gene Fusion
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Humans
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / genetics
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Microtubule-Associated Proteins / genetics*
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Molecular Targeted Therapy
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / therapeutic use*
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Pyrazoles / adverse effects
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Pyrazoles / therapeutic use*
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Pyridines / adverse effects
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Pyridines / therapeutic use*
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Receptor Protein-Tyrosine Kinases / genetics*
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Serine Endopeptidases / genetics*
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Signal Transduction
Substances
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Cell Cycle Proteins
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Microtubule-Associated Proteins
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Protein Kinase Inhibitors
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Pyrazoles
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Pyridines
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Crizotinib
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ALK protein, human
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases
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EML4 protein, human
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Serine Endopeptidases