title: Anaplastic Lymphoma Kinase as a Therapeutic Target in Non-Small Cell Lung Cancer.
abstract: The therapeutic targeting of anaplastic lymphoma kinase (ALK) has been a burgeoning area of research since 2007 when ALK fusions were initially identified in patients with non-small cell lung cancer. The field has rapidly progressed through development of the first-generation ALK inhibitor, crizotinib, to an understanding of mechanisms of acquired resistance to crizotinib and is currently witnessing an explosion in the development of next-generation ALK inhibitors such as ceritinib, alectinib, PF-06463922, AP26113, X-396, and TSR-011. As with most targeted therapies, acquired resistance appears to be an inevitable outcome. Current preclinical and clinical studies are focused on the development of rational therapeutic strategies, including novel ALK inhibitors, as well as rational combination therapies to maximize disease control by delaying or overcoming acquired therapeutic resistance. This review summarizes the existing clinical data and ongoing research pertaining to the clinical application of ALK inhibitors in patients with non-small cell lung cancer.
authors.affiliation: From the Departments of *Medicine and †Cancer Biology, Vanderbilt University Medical Center, and ‡Vanderbilt-Ingram Cancer Center, Nashville, TN.
authors.forename: Wade T
authors.initials: WT
authors.lastname: Iams
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lovly
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases