title: Targeting ALK in patients with advanced non small cell lung cancer: biology, diagnostic and therapeutic options.
abstract: The discovery of EML4-ALK fusion gene in a subgroup of patients with lung adenocarcinoma led to the development of a new class of agents, the ALK inhibitors, and dramatically improved the clinical outcome of these patients. The striking results from clinical trials with crizotinib, the first ALK inhibitor evaluated, allowed the accelerated approval of crizotinib from the USA Food and Drug Administration (FDA). Despite the high initial results, patients acquire resistance to crizotinib, and different next generation ALK kinase inhibitors have been developed. In the current review, we will analyze the biology of EML4-ALK gene, the acquired resistance mechanisms to crizotinib, the therapeutic strategies, currently under evaluation, designed to overcome crizotinib resistance, and the open issues that need to be addressed in order to improve outcome in ALK+ Non Small Cell Lung Cancer (NSCLC) patients.
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy. Electronic address: chiaralazzari07@gmail.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lazzari
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Spitaleri
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Catania
authors.affiliation: European Institute of Oncology, Division of Pathology, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Barberis
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Noberasco
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Mariacarmela
authors.initials: M
authors.lastname: Santarpia
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Delmonte
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Toffalorio
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Conforti
authors.affiliation: European Institute of Oncology, Division of Thoracic Oncology, Italy.
authors.forename: Tommaso Martino
authors.initials: TM
authors.lastname: De Pas
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology*; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology*
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Crizotinib; EML4-ALK fusion gene; Non Small Cell Lung Cancer