title: Crizotinib  in the treatment of non-small-cell lung cancer.
abstract: BACKGROUND
  Recent progress in identifying distinct subsets of lung cancer, based on critical driver mutations, has led to increasingly focused efforts in the development of selectively targeted therapies. The fusion oncogene, echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK), is present in approximately 5% of non-small-cell lung cancer (NSCLC) tumors. Crizotinib is an oral tyrosine kinase inhibitor (TKI), which silences the protein product of the ALK fusion gene and has recently been approved for the treatment of NSCLC aberrantly expressing ALK. Emerging data suggest that crizotinib may also have activity in other subsets of lung cancer, including tumors demonstrating amplification or mutation of the MET oncogene, or translocation of the ROS1 oncogene.
  
  
  METHODS
  This paper gives an overview of the molecular pathogenesis of ALK-associated NSCLC. It also reviews the pharmacokinetic and pharmacodynamic data on crizotinib and outlines the preclinical and clinical studies leading to the approval of crizotinib. In addition, it discusses its role in the treatment of NSCLC expressing ALK.
  
  
  CONCLUSIONS
  Crizotinib represents the newest example of a focused strategy for drug development in lung cancer, based on identification and targeted inhibition of critical tumor-specific driver mutations. Crizotinib has demonstrated efficacy against ALK-rearranged NSCLC, and has potential for broader application in select subsets of lung cancer.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Forde
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077547:Crizotinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib