喉癌对EGFR靶向药物的耐药一直困扰着喉癌治疗手段的革新。前期工作中我们发现喉癌在Cetuximab作用后EGFR表达上调，并激活PI3K-Akt信号通路，从而介导耐药。进一步结合喉癌发病的性别差异，发现在过度表达EGFR的喉癌组织中亦存在ERα36的过表达，两者呈显著正相关，且过表达ERα36的喉癌细胞较ERα36阴性的而言，其对Cetuximab的敏感性明显降低，由此我们推测在喉癌中ERα36的过度表达是否参与对EGFR表达的正向反馈，并激活下游Akt通路的活性，进而介导耐药。即Cetuximab的耐药是否通过ERα36参与EGFR信号通路中Src-PI3K-Akt的旁路激活产生交互调控作用。故在前期成功构建ERα36阳性的人喉癌移植瘤动物模型的基础上，拟从细胞、动物及临床水平探讨Src-PI3K-Akt通路相关分子对耐药机制的表达调控作用，为进一步联合靶点治疗提供理论依据。

Drug resistance of laryngeal cancer to EGFR targeting drugs has been plaguing the innovation of therapeutic methods for laryngeal cancer. In previous studies, we found that the expression of EGFR in laryngeal squamous cell carcinoma was up-regulated after Cetuximab treatment, and PI3K-Akt signaling pathway was activated to promote cell proliferation, which led to drug resistance. However, the specific regulatory mechanism is still unclear. In further studies, we studied the significant gender differences in the pathogenesis of laryngeal cancer.Considering that ERa36 is over-expressed in laryngeal cancer tissues with over-expression of EGFR, and the downstream of EGFR also activates PI3K-Akt signaling pathway, we speculate whether resistance to Cetuximab participates in the interaction of PI3K-AKt activation in EGFR signaling pathway through ERa36 in laryngeal cancer tumors associated with sex hormone expression. Src may be a key regulator of the interaction between EGFR and ERa36. In this study, we investigated the expression of src-PI3K-Akt pathway related molecules and their interaction with ER and EGFR at the cellular, animal and clinical levels, and explored the mechanism of resistance of laryngeal cancer to EGFR targeted drugs,providing a theoretical basis for further combined target therapy.