title: Anaplastic lymphoma kinase as a therapeutic target.
abstract: BACKGROUND
  Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, has been initially identified through its involvement in chromosomal translocations associated with anaplastic large cell lymphoma. However, recent evidence that aberrant ALK activity is also involved in an expanding number of tumor types, such as other lymphomas, inflammatory myofibroblastic tumor, neuroblastomas and some carcinomas, including non-small cell lung carcinomas, is boosting research progress in ALK-targeted therapies.
  
  
  METHODS
  The first aim of this review is to describe current understandings about the ALK tyrosine kinase and its implication in the oncogenesis of human cancers as a fusion protein or through mutations. The second goal is to discuss its interest as a therapeutic target and to provide a review of the literature regarding ALK inhibitors. Mechanisms of acquired resistance are also reviewed.
  
  
  CONCLUSIONS
  Several ALK inhibitors have recently been developed, offering new treatment options in tumors driven by abnormal ALK signaling. However, as observed with other tyrosine kinase inhibitors, resistance has emerged in patients treated with these agents. The complexity of mechanisms of acquired resistance recently described suggests that other therapeutic options, including combination of ALK and other kinases targeted drugs, will be required in the future.
authors.affiliation: Centre de Recherche en Oncologie Expérimentale, Institut de Recherche Pierre Fabre, Toulouse, Cedex 4, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Kruczynski
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases