title: Treatment modalities for advanced ALK-rearranged non-small-cell lung cancer.
abstract: The ALK gene plays a key role in the pathogenesis of non-small-cell lung cancer (NSCLC). Patients with NSCLC harboring an ALK-rearrangement represent the second oncogene addiction to be identified in this disease. Crizotinib was the first ALK inhibitor showing pronounced clinical activity, and is now a reference treatment for ALK-positive NSCLC disease. However, despite initial impressive responses to crizotinib, acquired resistance almost invariably develops within 12 months. The pressing need for effective second-line agents has prompted the rapid development of next-generation ALK inhibitors. These agents, notably ceritinib and alectinib as the most developed, have a higher potency against ALK than crizotinib, along with activity against tumors harboring crizotinib-resistant mutations and potentially improved CNS penetration.
authors.affiliation: Medical Oncology Department, Gustave Roussy, 114 Rue Édouard Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Ivana
authors.initials: I
authors.lastname: Sullivan
authors.affiliation: Medical Oncology Department, Gustave Roussy, 114 Rue Édouard Vaillant, 94805 Villejuif Cedex, France.
authors.forename: David
authors.initials: D
authors.lastname: Planchard
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D059039:Standard of Care; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK-rearrangement; CNS disease; alectinib; ceritinib; crizotinib; crizotinib-resistance; non-small-cell lung cancer