摘要
EML4-ALK是肺癌诱发基因之一,属于融合基因,2007年由日本学者首次报道。在非小细胞肺癌(non-small-celllung carcinoma,NSCLC)患者中EML4-ALK表达阳性率约为3%～8%。EML4-ALK融合基因存在多种不同结构的变异体,其中3种变异体占大多数,其他变异体相对较少。目前尚无标准的、快速简便的检测EML4-ALK的方法,使其临床应用推广受到限制,有待进一步研究。新近的临床研究发现,EML4-ALK阳性率和患者是否吸烟高度相关,也与年龄、腺癌以及表皮生长因子受体(epidermal growth factor receptor,EGFR)和KRAS基因是否突变等因素相关。其中不吸烟或轻度吸烟的NSCLC患者EML4-ALK阳性率高达9.4%,而在吸烟的患者中其阳性率只有2.9%,两者存在显著性差异。EML4-ALK表达阳性与EGFR、KRAS突变呈负相关。在NSCLC患者中EML4-ALK表达和EGFR、KRAS突变很少同时存在。EML4-ALK的抑制剂TAE684和PF02341066等目前已进入Ⅲ期临床试验,前期研究取得了较好的疗效。EML4-ALK现已成为NSCLC治疗的新靶点,EML4-ALK抑制剂为肺癌的个体化治疗提供了新的可选择方案,也可作为不能耐受化疗的患者的治疗药物。
EML4-ALK is a lung cancer-induced fusion gene, which was first discovered in Japan in 2007. Studies show that the positive rate of EML4-ALK is about 3%-8% in patients with non-small-cell lung cancer （NSCLC）. Multiple EML4-ALK variants have been identified in NSCLC, of which 3 make up the majority. Currently, a major issue is to define a best way to determine the presence of EML4-ALK in lung tumors, which has largely limited its clinical application. The positive rate of EML4-ALK is found to be correlated with smoking, age, adenocarcinoma, EGFR, and KRAS mutation, 9.4% in non- or light-smokers, significantly higher than 2.9% in smokers. The expression of EML4-ALK is negatively correlated with EGFR and KRAS mutations, which are mutually exclu- sive in NSCLC patients. ALK inhibitors, including TAE684 and PF02341066, have exhibited fair efficacy and are now under stage-llI clinical trials. EML4-ALK has become a new therapeutic target for NSCLC, and ALK inhibitors have provided new options for the indi- vidualized treatment of lung cancer, and brought new hope for those intolerant to chemotherapy.
出处
《医学研究生学报》
CAS
北大核心
2012年第2期200-203,共4页
Journal of Medical Postgraduates
基金
江苏省自然科学基金(BK2008326)
江苏省医学重点人才基金(RC2007113)
