摘要
目的：总结近年来有关非小细胞肺癌（non—smallcelllungcancer，NSCLC）表皮生长因子受体一酪氨酸激酶抑制剂（epidermalgrowth{actorreceptor-tyrosinekinaseinhibitors，EGFR—TKIs）获得性耐药相关分子机制的研究进展。方法：应用CNKI和PubMed数据库检索系统，以“非小细胞肺癌、EGFR—TKIs和获得性耐药”等为关键词，检索2005—01～2013-06相关文献，共检索到202条文献，纳入标准：1）公开发表和未公开发表的一次文献；2）文章内容提示有EGFR—TKIs获得性耐药的基础与临床研究报道；3）分析资料完整，至少有1个对照组；4）研究中有一定含量的样本，并进行统计学分析。剔除标准：1）无对照组文献；2）统计方法不恰当；3）重复报告。最后纳入分析30篇文献。结果：靶向治疗在NSCLC的治疗中取得了明显疗效。一线使用EGFR—TKIs的患者的总生存期可达2年。但即使对于EGFR—TKIs高度敏感的患者，在经过中位生存期7～9个月之后也会发生获得性耐药，主要机制有EGFR第二位点T790M二次突变以及MET的扩增等。目前针对这些机制有很多新药，如BIBW2992、ARQ197和克唑替尼等，但其有效率及安全性等仍处于探索阶段。结论：NSCLC患者对EGFR—TKIs获得性耐药机制仍在不断探索中，目前针对其机制的新型抑制剂的多项临床实验也正在进行。
OBJECTIVE：To summarize the progress of studies of molecular mechanisms of acquired resistance to EG- FR-TKIs in recent years. METHODS： PubMed and CNKI database retrieval system were searched, and the key words were ＂NSCLC,EGFR-TKIs,Acquired Drug Resistance＂ and so on,from 2005-01 to 2013-06. Totally 202 literatures were retrieved. The inclusion criteria was as follows： open published and unpublished literature; the contents of the article prompted with acquired resistance to EGFR-TKIs, basic and clinical researches reported; the completed analysis which contained at least one control group; some contents of the sample in the study were analyzed statistically. Exclusion crite- ria：literature without control group; inappropriate statistical methods; duplicate reported. Finally 30 literature were ana- lyzed. RESULTS： Target therapy in the treatment of NSCLC has achieved a noticeable effect. The overall survival of pa- tients who use EGFR-TKIs as first-line treatment is up to 2 years. But patients who even highly sensitive to EGFR-TKIs, also acquired resistance after a median survival of 7--9 months. The main mechanisms are EGFR secondary to T790M mu- tation and MET amplification. There are a lot of new drugs for these mechanisms,such as like BIBW 2992, ARQ 197 ,Cr- izotinib,etc. , but their efficiency and security is still at the exploratory stage. CONCLUSION： Mechanisms of acquired re- sistance to EGFR-TKIs are still at the exploratory stage,and a number of clinical trials of its novel mechanism inhibitors are under way.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2013年第18期1450-1454,共5页
Chinese Journal of Cancer Prevention and Treatment
