肺癌发病与死亡率逐年攀升，虽一代EGFR-TKIs对晚期EGFR突变肺腺癌疗效确切，但耐药不可避免。二代药物毒副反应重，同样耐药，疗效有限。以奥希替尼（AZD9291）为代表的三代EGFR-TKIs可克服前两代因T790M突变所致耐药，但对其自身耐药无有效对策，故延长三代药物疗效十分重要。中医认为，靶向药物属热毒，耗气伤阴，经EGFR-TKIs治疗易致气阴两虚而耐药。南方红豆杉能清热解毒、消积散结，延缓疾病进展，课题组前期研究表明其能抑制EGFR及下游PI3K/AKT、MEK/ERK、JAK/STAT通路与HGF/MET旁路激活。文献研究表明MEK抑制剂等可克服AZD9291耐药，结合临床我们推测南方红豆杉通过作用MEK/ERK等多条通路克服其耐药。本课题拟从体内外途径，采用生物信息分析、siRNA、过表达、qPCR等技术，研究其克服第三代EGFR-TKIs获得性耐药的机制，诠释临床疗效。

With the rate of incidence and mortality of lung cancer increasing annually, the first generation of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) are effective for the advanced lung adenocarcinoma patients with EGFR mutation, but the resistance to EGFR-TKIs is unavoidable. The second generation of the EGFR-TKIs have heavy side effects, similar resistance and limited activities. AZD9291, the representative of the third generation of EGFR-TKIs, can overcome the acquired resistance induced by T790M mutation after the former generation EGFR-TKIs. Unfortunately, there still haven’t strategies to overcome resisitance to AZD9291. Therefore, it is important to prolong the activities of the third generation of EGFR-TKIs. Chinese Traditional Medicine believes in that EGFR-TKIs have characteristic of toxic heat and can damage Qi and Yin, which is the main pathogenesis after EGFR-TKIs maintenance therapy. The Qi and Yin deficiencies can cause resistance to EGFR-TKIs. Taxus chinensis var.mairei has the activities of heat clearance, detoxification, elimination and dissipation etc, preventing the disease from progression. The results of our previous researches indicate that Taxus chinensis var.mairei can inhibite the activation of EGFR and downstream signal pathways PI3K/AKT, MEK/ERK, JAK/STAT and bypass ways HGF/MET. The literature indicates the MEK inhibitors etc. can overcome resisitance to AZD9291. Based on the clinical experiences, we think that the Taxus chinensis var.mairei can overcome resistance to the third generation of EGFR-TKIs through inhibition of multiple signal pathways such as MEK/ERK etc. Our further studies intends to explore the mechanisms of Taxus chinensis var.mairei overcoming the drug acquired resistance to the third generation of EGFR-TKIs by molecular biology methods of cell culture, animal model building, bioinformatic analysis, siRNA, overexpression, qPCR etc. These results will be helpful to further clinical practices.