Liao Bin-Chi, Lin Chia-Chi, Shih Jin-Yuan, Yang James Chih-Hsin
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan.
Ther Adv Med Oncol. 2015 Sep;7(5):274-90. doi: 10.1177/1758834015590593.
Rearrangements in anaplastic lymphoma kinase (ALK) gene and echinoderm microtubule-associated protein-like 4 (EML4) gene were first described in a small portion of patients with non-small cell lung cancer (NSCLC) in 2007. Fluorescence in situ hybridization is used as the diagnostic test for detecting an EML4-ALK rearrangement. Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC in 2011. Several mechanisms of acquired resistance to crizotinib have recently been reported. Second-generation ALK inhibitors were designed to overcome these resistance mechanisms. Two of them, ceritinib and alectinib, were approved in 2014 for advanced ALK-positive NSCLC in the US and Japan, respectively. Heat shock protein 90 (Hsp90) inhibitors also showed activity against ALK-positive NSCLC. Here we review the recent development of crizotinib, ceritinib, alectinib and other second-generation ALK inhibitors as well as Hsp90 inhibitors. We also discuss management strategies for advanced ALK-positive NSCLC.
间变性淋巴瘤激酶（ALK）基因和棘皮动物微管相关蛋白样4（EML4）基因的重排在2007年首次在一小部分非小细胞肺癌（NSCLC）患者中被描述。荧光原位杂交被用作检测EML4-ALK重排的诊断试验。克唑替尼，一种ALK抑制剂，在治疗晚期ALK阳性NSCLC方面有效，并且美国食品药品监督管理局在2011年批准其用于治疗ALK阳性NSCLC。最近报道了几种对克唑替尼获得性耐药的机制。第二代ALK抑制剂旨在克服这些耐药机制。其中两种，色瑞替尼和阿来替尼，分别于2014年在美国和日本被批准用于治疗晚期ALK阳性NSCLC。热休克蛋白90（Hsp90）抑制剂也显示出对ALK阳性NSCLC的活性。在此我们综述克唑替尼、色瑞替尼、阿来替尼及其他第二代ALK抑制剂以及Hsp90抑制剂的近期进展。我们还讨论晚期ALK阳性NSCLC的管理策略。
