title: Crizotinib in the treatment of non--small-cell lung cancer.
abstract: An anaplastic lymphoma kinase (ALK) translocation giving rise to activated ALK tyrosine kinase is present in approximately 5% of non-small-cell lung cancers (NSCLCs). Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, met proto-oncogene, and c-ros oncogene 1 (ROS1). It was recently approved in several countries for the treatment of patients with advanced, ALK-rearranged NSCLC. In 2012, results from the first phase III trial showing superiority of crizotinib compared with standard chemotherapy in second-line treatment of ALK-positive NSCLC were presented. Furthermore, crizotinib was recently shown to be active in ROS1-rearranged NSCLC. Here, we give an overview of the molecular pathogenesis of ALK-rearranged NSCLC, the pharmacokinetic and pharmacodynamic properties of crizotinib, and clinical trials of crizotinib for ALK-rearranged NSCLC.
authors.affiliation: Department Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland. sacha.rothschild@usb.ch
authors.forename: Sacha I
authors.initials: SI
authors.lastname: Rothschild
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077547:Crizotinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*
chemical_list: C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib
keywords: Anaplastic lymphoma kinase; EML4-ALK; ROS1; Targeted therapy; Tyrosine kinase inhibitor