期刊
EXPERT REVIEW OF ANTICANCER THERAPY
卷 11, 期 11, 页码 1677-1687出版社
TAYLOR & FRANCIS LTD
DOI: 10.1586/ERA.11.157
关键词
ALK rearrangements; crizotinib; EML4-ALK gene; lung adenocarcinoma; NSCLC
类别
The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in non-small-cell lung cancer (NSCLC) populations susceptible to targeted inhibition. It consists of a small inversion in the short arm of chromosome 2 between exon 20 of the ALK gene and different exons of the echinoderm microtubule-associated protein-like (EML4) gene. This translocation leads to a chimeric protein with constitutive activation of ALK that possesses an oncogenic activity demonstrated both in vitro and in vivo. Other rare translocation partners for ALK other than EML4 may be found in lung cancers, including TRK-fused gene (TFG) and kinesin family member 5B (KIF5B). ALK-positive patients represent 5-6% of all NSCLCs and they seem to have particular clinicopathological and molecular features. Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC. This article will present knowledge on the characteristics of ALK-positive patients, discuss the different methods of ALK rearrangement detection and focus on clinical results of crizotinib.
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