Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
Cancer Cell. 2010 Dec 14;18(6):548-51. doi: 10.1016/j.ccr.2010.11.033.
It was only 3 years ago that an acquired translocation of EML4 with ALK leading to the expression of an EML4-ALK oncoprotein in non-small cell lung cancer (NSCLC) was reported. Tumor cells expressing EML4-ALK are "addicted" to its continued function. Now, crizotinib, an oral ALK inhibitor, is demonstrated to provide dramatic clinical benefit with little toxicity in patients having such advanced NSCLC, and a mechanism of clinical resistance to crizotinib is identified. Such therapy "targeted" at oncogenic proteins provides "personalized" medicine and prompts genome-wide mutation analysis of human tumors to find other therapeutic targets.
仅在 3 年前，有研究报道了非小细胞肺癌（NSCLC）中 EML4 与 ALK 的获得性易位导致 EML4-ALK 癌蛋白的表达。表达 EML4-ALK 的肿瘤细胞“依赖”其持续发挥功能。目前，ALK 抑制剂克唑替尼在具有这种晚期 NSCLC 的患者中表现出显著的临床获益且毒性较小，并且鉴定出对克唑替尼产生临床耐药的机制。这种针对致癌蛋白的“靶向”治疗提供了“个体化”药物，并促使对人类肿瘤进行全基因组突变分析以寻找其他治疗靶点。
