EGFR TKIs获得性耐药严重限制了其长期疗效，是肺腺癌治疗领域亟待解决的难题。目前已发现PRMT5可影响多种抗肿瘤药物的敏感性，但是其与肺腺癌EGFR TKIs获得性耐药的关系尚不明确。我们前期研究发现，PRMT5在EGFR TKIs获得性耐药肺腺癌组织中表达显著增高；过表达PRMT5可引起AHR上调，产生EGFR TKIs耐药。由此我们提出假说：PRMT5可通过促进AHR表达参与肺腺癌EGFR TKIs获得性耐药的发生。本课题拟利用生物信息学分析和分子生物学等方法，探讨PRMT5-AHR途径对肺腺癌EGFR TKIs获得性耐药的影响，明确PRMT5通过组蛋白甲基化修饰调控AHR表达的机制，并在临床组织和动物模型中验证。本研究将阐明PRMT5在肺腺癌EGFR TKIs获得性耐药中的作用机理，并揭示其临床意义，为克服EGFR TKIs获得性耐药难题提供新的理论基础和潜在靶点。

Acquired resistance to EGFR TKIs inevitably occurs and severely impairs the clinical efficacy of lung adenocarcinoma targeted therapy. It is an urgent problem in lung adenocarcinoma management and treatment. PRMT5 has been found to affect the sensitivity of a number of antitumor drugs, but its association with acquired resistance to EGFR TKIs in lung adenocarcinoma is unclear. Our previous studies indicated that the expression of PRMT5 in the acquired EGFR TKIs-resistant lung adenocarcinoma was significantly increased. Overexpression of PRMT5 could cause upregulation of AHR, and lead to resistance to EGFR TKIs. Thus, we propose a hypothesis that, in lung adenocarcinoma, PRMT5 may be involved in the development of acquired resistance to EGFR TKIs by regulating AHR expression. This subject aims to illustrate the pivotal role of PRMT5-AHR pathway in acquired resistance to EGFR TKIs via bioinformatics analysis and molecular biology methods, uncover the mechanism of PRMT5 regulating AHR expression by means of histone methylation, and further validate hypothesis above in clinical tissues and animal models. This study will explore the effects of PRMT5 in the acquired resistance to EGFR TKIs in lung adenocarcinoma, illustrate its clinical implications, providing a brand-new insight and potential drug targets for overcoming the urgent problem of acquired resistance to EGFR TKIs.