西妥昔单抗治疗非小细胞肺癌耐药机制的研究进展

Research progress of resistance mechanisms in the treatment of non-small cell lung cancer with cetuximab

目的:总结国内外关于西妥昔单抗治疗非小细胞肺癌中耐药机制的研究进展。方法:应用Medline、PubMed、EMBASE及中国生物医学文献数据库检索系统,以"西妥昔单抗、非小细胞肺癌、表皮生长因子受体及耐药机制"为关键词,检索1990-01-2010-02的相关文献。纳入标准:1)EGFR旁路信号传导通路与西妥昔单抗抵抗的关系;2)非小细胞肺癌患者EGFR基因突变与西妥昔单抗耐药;3)EGFR下游信号转导通路的活化与西妥昔单抗抵抗的关系。根据纳入标准分析34篇文献。结果:由于表皮生长因子受体(EGFR)调节多种细胞功能,EGFR抑制剂西妥昔单抗耐药现象可能与多个传导通路紊乱有关,包括旁路信号途径的激活、受体突变、配体自分泌/旁分泌的产生以及下游信号蛋白的组成性活化。结论:目前对西妥昔单抗产生耐药的确切机制尚不明确,要想解决其耐药问题,进一步提高西妥昔单抗治疗非小细胞肺癌的疗效,尚需进行更多项进一步的临床和基础研究来加以证实。

OBJECTIVE：To sum up the advances in the mechanisms of resistance in the cetuximab treatment of non-small cell lung cancer in domestic and foreign research.METHODS：＂Cetuximab,non-small cell lung cancer,EGFR,resistance,and mechanism＂ were searched as key words in the databases of Medline,PubMed,EMBASE and CbmWeb/CbmWin.from 01-1990 to 02-2010.Choice criteria：1）the relationship between the bypass EGFR signaling pathway and cetuximab resistance; 2）non-small cell lung cancer patients with EGFR gene mutation and cetuximab-resistant; 3）EGFR downstream signal transduction pathway activation and cetuximab resistance.By extraction according to the choice criteria,among roughing thousands of the related articles,34 papers were analyzed.RESULTS：As the EGFR regulates a variety of cell functions,the resistance phenomenon may be related to the disturbance of multiple pathways,including the bypass signal pathway activation,receptor mutation,ligand autocrine/paracrine generation and constitutive cation of downstream signaling protein.CONCLUSIONS：Today,the exact mechanisms of cetuximab resistance still are not achieved.In order to resolve this problem and improve the effect of cetuximab in the treatment of non-small cell lung cancer,more clinical and basic research should be conducted.