The advancement of genetic research has changed the treatment management of non-small cell lung cancer (NSCLC) and opened the era of personalized medicine. Currently, three generations of EGFR tyrosine kinase inhibitors (TKIs) are used in the treatment of NSCLC patients with activating mutations in theEGFRgene, and ongoing clinical trials examine the safety and effectiveness of new third and fourth generations. Osimertinib, a third generation of TKIs that binds irreversibly to abnormal tyrosine kinase, may be applied in various indications in patients with NSCLC: (i) in the second and subsequent lines of therapy in patients with resistance to first-generation or second-generation EGFR TKIs, (ii) in the first line of treatment in monotherapy in NSCLC patients with frequent or rareEGFRmutations, (iii) in combination with chemotherapy in patients with locally advanced or metastatic NSCLC with frequentEGFRmutations, (iv) in consolidation therapy in patients with locally advanced NSCLC who had previously received chemoradiotherapy, (v) in adjuvant treatment of NSCLC patients with stage IB—IIIA undergoing radical surgical resection. Despite the high efficacy of osimertinib in NSCLC patients harboringEGFRmutations, resistance driven in EGFR-dependent or EGFR-independent mechanisms may occur. Since resistance to osimertinib is poorly understood, the following review presents the overview of resistance mechanisms to osimertinib, methodological approaches for the resistance diagnosis, and the up-to-date treatment possibilities for overcoming the resistance process.
遗传学研究的进展改变了非小细胞肺癌（NSCLC）的治疗管理，开启了精准医疗时代。目前，针对携带EGFR基因激活突变的NSCLC患者，已有三代EGFR酪氨酸激酶抑制剂（TKIs）应用于临床，而新型第三代及第四代药物的安全性与有效性仍在临床试验中持续验证。奥希替尼作为第三代TKIs，能不可逆地结合异常酪氨酸激酶，其在NSCLC患者中的适应症涵盖多个层面：（一）用于对第一代或第二代EGFR TKIs产生耐药患者的二线及后续治疗；（二）作为单药一线治疗携带常见或罕见EGFR突变的NSCLC患者；（三）联合化疗治疗携带常见EGFR突变的局部晚期或转移性NSCLC患者；（四）作为局部晚期NSCLC患者既往放化疗后的巩固治疗；（五）用于IB-IIIA期接受根治性手术切除的NSCLC患者辅助治疗。尽管奥希替尼对携带EGFR突变的NSCLC患者具有显著疗效，但通过EGFR依赖性或非依赖性机制产生的耐药性仍可能发生。鉴于目前对奥希替尼耐药机制的认识尚不充分，本综述系统阐述了奥希替尼的耐药机制、耐药诊断方法学路径以及当前克服耐药过程的治疗策略。
肿瘤(癌症)患者之家