title: Anaplastic lymphoma kinase as a new target for the treatment of non-small-cell lung cancer.
abstract: The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in non-small-cell lung cancer (NSCLC) populations susceptible to targeted inhibition. It consists of a small inversion in the short arm of chromosome 2 between exon 20 of the ALK gene and different exons of the echinoderm microtubule-associated protein-like (EML4) gene. This translocation leads to a chimeric protein with constitutive activation of ALK that possesses an oncogenic activity demonstrated both in vitro and in vivo. Other rare translocation partners for ALK other than EML4 may be found in lung cancers, including TRK-fused gene (TFG) and kinesin family member 5B (KIF5B). ALK-positive patients represent 5-6% of all NSCLCs and they seem to have particular clinicopathological and molecular features. Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC. This article will present knowledge on the characteristics of ALK-positive patients, discuss the different methods of ALK rearrangement detection and focus on clinical results of crizotinib.
authors: Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43100 Parma, Italy. mtiseo@ao.pr.it
authors: Marcello
authors: M
authors: Tiseo
authors: Francesco
authors: F
authors: Gelsomino
authors: Marco
authors: M
authors: Bartolotti
authors: Paola
authors: P
authors: Bordi
authors: Melissa
authors: M
authors: Bersanelli
authors: Giulio
authors: G
authors: Rossi
authors: Andrea
authors: A
authors: Ardizzoni
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* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D000077547:Crizotinib; D005091:Exons; D015321:Gene Rearrangement; D006801:Humans; D016547:Kinesins / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011506:Proteins / Q000235:genetics; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D000077547:Crizotinib; D016547:Kinesins; D008869:Microtubule-Associated Proteins; D047428:Protein Kinase Inhibitors; D011506:Proteins; D011720:Pyrazoles; D011725:Pyridines; D020794:Receptor Protein-Tyrosine Kinases; D012697:Serine Endopeptidases; C488101:KIF5B protein, human; C096163:TFG protein, human; D033921:Vesicular Transport Proteins; C000626173:ALK protein, human; C415585:EML4 protein, human