肺癌是嚴(yán)重威脅人類健康的重大疾病，而非小細(xì)胞肺癌（non-small cell lung cancer，NSCLC）則占所有類型肺癌的85%以上。目前，“個體化給藥”是改善晚期NSCLC患者治療效果的一條前景良好的途徑。2011年8月，美國食品和藥物管理局（FDA）批準(zhǔn)了克里唑替尼（crizotinib），一種ALK/MET/ROS1抑制劑，用于治療間變性淋巴瘤激酶（ALK）基因重排的非小細(xì)胞肺癌，同時還批準(zhǔn)了一種ALK熒光原位雜交法檢測試劑盒，作為伴侶診斷試劑，用于ALK重排的非小細(xì)胞肺癌的檢測。隨后，克里唑替尼被作為一種ALK和MET抑制劑開發(fā)，用于治療由ALK和MET 突變驅(qū)動的其他類型的腫瘤。最近已經(jīng)證實在ROS1重排的非小細(xì)胞肺癌中克里唑替尼是一種有效的ROS1抑制劑，并且未來可能用于ROS1基因重排腫瘤的臨床治療。對克里唑替尼的設(shè)計開發(fā)、治療ALK重排的NSCLC的的臨床應(yīng)用、藥物不良反應(yīng)以及相應(yīng)的疾病診斷檢測方法進(jìn)行了回顧，以期為NSCLC的靶向治療藥物的研究和開發(fā)提供參考。

Lung cancer is the major disease seriously threaten human health, in which non-small cell lung cancer (NSCLC) account to more than 85%. At present, “personalized administration” is a promising approach that could improve the treatment outcomes in patients with NSCLC. In August 2011, crizotinib was approved by the US Food and Drug Administration (FDA) for the treatment of anaplastic lymphoma kinase (ALK)-rearranged NSCLC as an ALK/MET/ROS1 inhibitor. At the same time, an ALK companion diagnostic fluorescence in situ hybridization assay was approved by FDA as an accompanied reagent for the detection of ALK-rearranged NSCLC. Crizotinib was developed as an ALK and MET inhibitor to treat other tumor types driven by alteration in ALK and MET. Recently, it has been shown that crizotinib is a kind of effective ROS1 inhibitor on ROS1-rearranged NSCLC, and it may be used in the clinical treatment of ROS1-rearranged tumors. This article reviewed the design and development of crizotinib, its clinical application in ALK-rearranged NSCLC, its adverse drug effects, and the dignaose methods for the disease, in order to support the references to the research and development of the targeting drug for the treatment of NSCLC.