Iwama Eiji, Okamoto Isamu, Harada Taishi, Takayama Koichi, Nakanishi Yoichi
Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan ; Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan.
Onco Targets Ther. 2014 Mar 5;7:375-85. doi: 10.2147/OTT.S38868. eCollection 2014.
The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK) was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%-5% of non-small-cell lung cancer (NSCLC) cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers. A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors. We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC.
2007年，棘皮动物微管相关蛋白样4与间变性淋巴瘤激酶（ALK）的融合被鉴定为肺癌的一种转化基因。这种基因重排占非小细胞肺癌（NSCLC）病例的2% - 5%，主要发生在年龄较轻、患有腺癌且从不吸烟或轻度吸烟的个体中。基于其在ALK重排阳性NSCLC患者中显著的临床活性，一种小分子ALK酪氨酸激酶抑制剂克唑替尼迅速获得了美国食品药品监督管理局的批准。下一代ALK抑制剂，如阿来替尼、LDK378和AP26113，也正在进行的临床试验中研发。此外，NSCLC患者中ALK重排检测方法的改进和验证将是ALK抑制剂最佳临床应用的关键。我们在此总结新ALK抑制剂开发以及ALK重排阳性NSCLC分子诊断方面的最新进展。
