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  • Title: Crizotinib in the management of advanced-stage non-small-cell lung cancer.
    Author: Loong HH, Mok K, Leung LK, Mok TS.
    Journal: Future Oncol; 2015; 11(5):735-45. PubMed ID: 25757678.
    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.
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