Advances in research on anaplastic lympgoma kinase inhibitors

doi:10.16085/j.issn.1000-6613.2016.12.035

Abstract

Abstract: Researchers have found that multiple oncogenic driver multations are closely related with the progression and prognosis of NSCLC. In the era of molecular targeted treatment,rearrangements in anaplastic lymphoma kinase(ALK)gene and echinoderm microtubule-associated protein-like 4(EML4)gene were applied in patients with non-small cell lung cancer(NSCLC). Crizotinib,an ALK inhibitor,is effective in treating advanced ALK-positive NSCLC,and the US Food and Drug Administration(FDA)approved it for treating ALK-positive NSCLC. Several mechanisms of acquired resistance to crizotinib have recently been reported. Second-generation ALK inhibitors were developed to overcome these resistance mechanisms and showed activity against ALK positive NSCLC. The latest development of crizotinib,ceritinib,alectinib etc. were reviewed.

Key words: non small cell lung cancer, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement, crizotinib

摘要： 研究发现非小细胞肺癌的形成与多种致癌突变密切相关，其中间变性淋巴瘤激酶重排备受关注，针对棘皮动物微管相关蛋白质4-间变性淋巴瘤激酶融合基因的抑制剂克唑替尼对于治疗晚期ALK阳性非小细胞肺癌患者是有效的，2011年获得美国食品药品监督管理局批准上市，但出现了耐药性，第二代间变性淋巴瘤激酶抑制剂的出现，克服了耐药机制，并显示出治疗非小细胞肺癌患者的活性。本论文按化学结构的不同介绍了克唑替尼、Ceritinib、Alectinib、Brigatinib、RXDX-101、PF-06463922、ASP3026、X-396、CEP-37440等间变性淋巴瘤激酶抑制剂及临床研究等，为非小细胞肺癌的靶向治疗药物的开发提供了参考。

关键词: 非小细胞肺癌, EML4-ALK基因重排, 克唑替尼

CLC Number:

TN41

CHEN Yalin, LI Wei, WANG Tianyang, ZHOU Xueqin, LIU Dongzhi. Advances in research on anaplastic lympgoma kinase inhibitors[J]. Chemical Industry and Engineering Progress, 2016, 35(12): 3985-3990.

陈雅琳, 李巍, 汪天洋, 周雪琴, 刘东志. 间变性淋巴瘤激酶抑制剂的研究进展[J]. 化工进展, 2016, 35(12): 3985-3990.

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