title: Crizotinib in the management of advanced-stage non-small-cell lung cancer.
abstract: ABSTRACT  Rearrangement of ALK gene has been identified as exerting a potent transforming effect as driver oncogene in patients with non-small-cell lung cancer (NSCLC). Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases. Its efficacy in ALK-rearranged NSCLC has been established. Crizotinib's effect on ROS1 receptor kinases and c-Met with relevance to NSCLC is also actively being explored. Resistance mechanisms such as secondary gatekeeper mutations in ALK gene and activation of other oncogenes have been identified to confer acquired resistance to crizotinib. This article reviews the pharmacological properties of crizotinib, preclinical and clinical results that led to its approval in ALK-positive NSCLC and current directions of clinical research in overcoming crizotinib resistance.
authors.affiliation: Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Herbert H
authors.initials: HH
authors.lastname: Loong
authors.forename: Kevin
authors.initials: K
authors.lastname: Mok
authors.forename: Linda K S
authors.initials: LK
authors.lastname: Leung
authors.forename: Tony S K
authors.initials: TS
authors.lastname: Mok
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000077547:Crizotinib; D019468:Disease Management; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met; C062333:ROS1 protein, human
keywords: EML4–ALK fusion; ROS1; acquired resistance; brain metastases; c-Met; crizotinib; non-small-cell lung cancer