title: Anaplastic Lymphoma Kinase Inhibitors in Non-Small Cell Lung Cancer.
abstract: Lung cancer is the leading cause of cancer death among both sexes in the United States and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Over the last several decades, there have been many advances in both surgical approaches and systemic therapies for the treatment of NSCLC, but the prognosis for advanced disease remains poor. New research, however, is exploring the use of targeted therapies for the treatment of NSCLC. The anaplastic lymphoma kinase (ALK) is involved in normal mammalian central nervous system development. A novel fusion gene involving ALK and the echinoderm microtubule-associated protein-like 4 (EML4) gene has been associated with approximately 5% of NSCLCs and is mutually exclusive of other oncogenic driver mutations. Targeted therapies against this ALK rearrangement are a relatively new treatment modality that aims to improve the prognosis of patients with late-stage disease. Two such drugs have Food and Drug Administration (FDA) approval currently: Crizotinib and Ceritinib. Many other ALK inhibitors are currently being studied in clinical trials as well. The authors aim to provide a comprehensive review of ALK inhibitors for use in NSCLC as well as the future directions and challenges to developing these targeted therapies.
authors.forename: David M
authors.initials: DM
authors.lastname: Straughan
authors.forename: Said C
authors.initials: SC
authors.lastname: Azoury
authors.affiliation: Thoracic and GI Oncology Branch, National Institutes of Health, Bathesda, MD 20892, USA. vivek.shukla@nih.gov.
authors.forename: Vivek
authors.initials: V
authors.lastname: Shukla
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D002986:Clinical Trials as Topic; D000077547:Crizotinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib