title: Targeting ALK: a promising strategy for the treatment of non-small cell lung cancer, non-Hodgkin's lymphoma, and neuroblastoma.
abstract: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that affects a number of biological and biochemical functions through normal ligand-dependent signaling. It has oncogenic functions in a number of tumors including non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma, and neuroblastoma when altered by translocation or amplification or mutation. On August 2011, a small molecule inhibitor against ALK, crizotinib, was approved for therapy against NSCLC with ALK translocations. As we determine the molecular heterogeneity of tumors, the potential of ALK as a relevant therapeutic target in a number of malignancies has become apparent. This review will discuss some of the tumor types with oncogenic ALK alterations. The activity and unique toxicities of crizotinib are described, along with potential mechanisms of resistance and new therapies beyond crizotinib.
authors.forename: Andres
authors.initials: A
authors.lastname: Morales La Madrid
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, IL, USA.
authors.forename: Andres Morales
authors.initials: AM
authors.lastname: La Madrid
authors.forename: Nicholas
authors.initials: N
authors.lastname: Campbell
authors.forename: Sonali
authors.initials: S
authors.lastname: Smith
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008957:Models, Genetic; D009154:Mutation; D009447:Neuroblastoma / Q000188:drug therapy*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases