title: The role of anaplastic lymphoma kinase inhibitors in the treatment of advanced nonsmall cell lung cancer.
abstract: OBJECTIVE
  Treatment of advanced nonsmall cell lung cancer (NSCLC) has rapidly changed over the last decade. On the basis of the progress made in cancer biology, the old-fashioned 'one size fits all' chemotherapeutic approach is shifting to a novel approach in which treatment choice is mainly based on the tumor's biological genotype. The aim of the present review is to describe the anaplastic lymphoma kinase (ALK) translocation as a prominent molecular driver aberration in NSCLC, its prognostic and predictive role, and the new available treatment options.
  
  
  RESULTS
  Crizotinib is a tyrosine kinase inhibitor of MET, ALK and ROS1. Its impressive clinical activity shown in a phase IB trial led to accelerated approval for patients with ALK-positive advanced NSCLC. More recently, a phase III trial confirmed the high activity of crizotinib in this subset of lung tumors. Many new-generation ALK inhibitors are currently also in clinical development.
  
  
  CONCLUSIONS
  ALK-positive NSCLC has emerged as a distinct, well defined subset of lung malignancies. The use of ALK inhibitors deeply impacts the therapy of patients harboring such translocation. Nevertheless, to date, several issues remain open, such as the most suitable screening and diagnostic method for the detection of ALK gene rearrangement and expression and particularly the mechanisms of acquired resistance for further clinical development of these agents.
authors: University of Colorado Cancer Center, Aurora, Colorado 80045, USA.
authors: Manolo
authors: M
authors: D'Arcangelo
authors: Murry W
authors: MW
authors: Wynes
authors: Fred R
authors: FR
authors: Hirsch
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases