title: The emerging role of ALK inhibitors in the treatment of advanced non-small cell lung cancer.
abstract: BACKGROUND
  Most NSCLC patients are diagnosed in the advanced stage of the disease. Recently, chemotherapeutic agents have reached a plateau of effectiveness. Increased understanding of cancer biology has revealed several potential therapeutic strategies that have led to marketing of new biologic agents. The echinoderm microtubule-associated protein like-4-anaplastic lymphoma kinase (EML4-ALK) fusion oncogene represents one of the newest molecular targets in NSCLC, identifying a subset of NSCLC patients characterized by distinct clinicopathological features.
  
  
  METHODS
  The available results concerning ALK inhibitors for the treatment of advanced NSCLC patients. An electronic search was used to retrieve the articles addressing this topic.
  
  
  CONCLUSIONS
  In a pivotal Phase I clinical trial, crizotinib (PF-02341066), a small-molecule ALK inhibitor, demonstrated impressive antitumor activity in the majority of NSCLC patients with ALK fusions. Phase III randomized trials investigating crizotinib in this subgroup of patients are ongoing. If the results from these large international trials confirm the efficacy of crizotinib in the subset of patients, the next few years could see the treatment of advanced NSCLC patients with ALK fusions. Specific inhibitors would realize the so called personalized medicine in subsets of this disease.
authors.affiliation: Giovanni Paolo II Oncology Institute, Medical Oncology Departement, 65, Viale Orazio Flacco, 70124 Bari, Italy. galetta@teseo.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pisconti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases