EML4-ALK 融合基因在非小细胞肺癌中的研究进展

肺癌是发病率和死亡率最高的恶性肿瘤,分子靶向治疗以其特异性高、副反应轻的特点正日益受到关注。近年来临床研究发现EML4-ALK融合基因是除EGFR突变及KRAS突变之外的另-个重要的酪氨酸激酶抑制剂的作用靶点,该融合基因在年轻、不吸烟或少吸烟、腺癌、无EGFR和KRAS突变的非小细胞肺癌患者中发生率较高,且该融合基因阳性者对酪氨酸激酶抑制剂耐药,对于ALK抑制剂(如克唑替尼)则有良好的治疗反应,关于该药的临床试验表明:总有效率达57%(46例确定为部分缓解,1例确定为完全缓解),估计6个月无进展生存概率为72%,常见的副反应是1、2级胃肠道反应。该基因及该药的发现为非小细胞肺癌患者带来了希望。

Research Progress of EML4-ALK Fusion Gene in Non-small Cell Lung Cancer

The morbidity and mortality of lung cancer is currently the highest in all the malignant tumors.Because of its higher specificity and milder side-effects,molecule target therapy in non-small cell lung cancer(NSCLC) is drawing concern at present.Recently clinical studies have found that EML4-ALK fusion gene is another important molecular target of tyrosine kinase inhibitors in addition to EGFR mutations and KRAS mutations.The fusion gene has higher morbidity in NSCLC patients who are young,never or light smoking history,adenocarcinomas,without EGFR and KRAS mutation.Although patients who harbor this mutation do not benefit from EGFR TKIs,they have shown good response to ALK inhibitor(for example: Crizotinib).Clinical trials about the drug have shown: the overall response rate was 57%(with 46 confirmed partial responses and 1 confirmed complete response),and the estimated probability of 6-month progression-free survival was 72%,grade 1 or 2 mild gastrointestinal effects are the common side effects.Discovery of the gene and the drug may bring new hope for the patients with NSCLC.