Srinivasamaharaj Srividya, Salame Bilal Khameze, Rios-Perez Jorge, Kloecker Goetz, Perez Cesar A
a Division of Medical Oncology and Hematology, James Graham Brown Cancer Center , University of Louisville , Louisville , KY , USA.
Expert Rev Anticancer Ther. 2016 Dec;16(12):1227-1233. doi: 10.1080/14737140.2016.1249857. Epub 2016 Nov 3.
The identification of anaplastic lymphoma kinase (ALK) gene rearrangements in subsets of non-small cell lung cancer patients has provided with unparalleled opportunities to hinder the progression of this disease through targeting the activity of these specific molecules. Unfortunately most patients develop disease progression in less than a year of treatment with crizotinib, the first-generation ALK-inhibitor. Areas covered: We review the resistance mechanisms to ALK inhibitors as well as an overview of the clinical activity of the alectinib, a second generation ALK inhibitor. Expert commentary: Second generation ALK inhibitors as alectinib and ceritinib can overcome crizotinib-resistant mutations and improve central nervous system control. Novel third-generation inhibitors and combination of agents give hope of achieving an even longer disease control in the next decade.
在非小细胞肺癌患者亚组中鉴定出间变性淋巴瘤激酶（ALK）基因重排，为通过靶向这些特定分子的活性来阻碍该疾病进展提供了前所未有的机会。不幸的是，大多数患者在使用第一代ALK抑制剂克唑替尼治疗不到一年的时间内就出现了疾病进展。涵盖领域：我们综述了对ALK抑制剂的耐药机制以及第二代ALK抑制剂阿来替尼的临床活性概况。专家评论：第二代ALK抑制剂如阿来替尼和色瑞替尼可以克服克唑替尼耐药突变并改善中枢神经系统控制。新型第三代抑制剂和联合用药有望在未来十年实现更长时间的疾病控制。
