表皮生长因子受体家族单克隆抗体耐药机制的研究进展

表皮生长因子受体（EGFR）家族广泛存在于体内各种细胞中,其异常活化与多种人类上皮组织肿瘤的发生、发展密切相关,因此已成为肿瘤治疗的重要靶点之一。目前靶向EGFR家族的药物包括小分子酪氨酸激酶抑制剂和单克隆抗体（简称单抗）类药物,特别是单抗类药物近年来在临床上获得了广泛的应用。但是,越来越多的临床资料表明,大量患者对这类药物表现出原发性耐药或获得性耐药。目前靶向EGFR家族单抗类药物产生耐药的原因主要包括：受体结构改变、血管生成、多种受体酪氨酸激酶的活化、EGFR的亚细胞定位、EGFR下游效应分子的持续激活和EGFR家族生长因子表达的上调等。本文就靶向EGFR家族单抗类药物耐药机制的研究进展进行综述。

Mechanisms of resistance to epidermal growth factor receptor family targeting monoclonal antibodies

The epidermal growth factor receptor （EGFR） family is ubiquitously expressed in various cell types. Aberrant ex- pression or activity of the EGFR has been identified as an etiological factor in the development and progression of many human epithelial tumors. Monoclonal antibodies （mAb） and small molecules tyrosine kinase inhibitor have been widely used to target the receptors. Both approaches have shown antitumor activity in clinical application, especially the mAb. However, increasing evidence suggests pri- mary and acquired resistance to mAb remain a major clinical problem. Several mechanisms of mAb-resistance have been reported, in- cludeing structural changes in EGFR family receptors, angiogenesis, activation of other receptor tyrosine kinases, subeellular localiza- tion of EGFR, constitutive activation of EGFR downstream effector molecules, and increased expression of EGFR family growth factors. This review summarizes the advance on mechanisms of resistance to EGFR family targeting antibodies.