间变性淋巴瘤激酶（ALK）和原癌基因酪氨酸蛋白激酶ROS1作为靶向治疗模式及克服克唑替尼耐药性的临床意义
ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance.
作者信息
Ye Mingxiang, Zhang Xinxin, Li Nan, Zhang Yong, Jing Pengyu, Chang Ning, Wu Jianxiong, Ren Xinling, Zhang Jian
机构信息
Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
出版信息
Oncotarget. 2016 Mar 15;7(11):12289-304. doi: 10.18632/oncotarget.6935.
During the past decade, more than 10 targetable oncogenic driver genes have been validated in non-small cell lung cancer (NSCLC). Anaplastic lymphoma kinase (ALK) and ROS1 kinase are two new driver genes implicated in ALK- and ROS1-rearranged NSCLC. Inhibition of ALK and ROS1 by crizotinib has been reported to be highly effective and well tolerated in these patients. However, resistance to crizotinib emerges years after treatment, and increasing efforts have been made to overcome this issue. Here, we review the biology of ALK and ROS1 and their roles in cancer progression. We also summarize the ongoing and completed clinical trials validating ALK and ROS1 as targets for cancer treatment. In the last section of the review, we will discuss the molecular mechanisms of crizotinib resistance and focus approaches to overcome it. This review describes an exciting new area of research and may provide new insights for targeted cancer therapies.
在过去十年中，超过10个可靶向的致癌驱动基因已在非小细胞肺癌（NSCLC）中得到验证。间变性淋巴瘤激酶（ALK）和ROS1激酶是与ALK和ROS1重排的NSCLC相关的两个新驱动基因。据报道，克唑替尼对ALK和ROS1的抑制在这些患者中具有高效性且耐受性良好。然而，治疗数年之后会出现对克唑替尼的耐药性，并且人们已做出越来越多的努力来克服这一问题。在此，我们综述ALK和ROS1的生物学特性及其在癌症进展中的作用。我们还总结了正在进行和已完成的将ALK和ROS1验证为癌症治疗靶点的临床试验。在综述的最后部分，我们将讨论克唑替尼耐药的分子机制以及克服耐药的重点方法。本综述描述了一个令人兴奋的新研究领域，并可能为靶向癌症治疗提供新的见解。
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