EGFR-TKIs治疗EGFR突变耐药NSCLC的治疗策略
Therapeutic Strategies for Overcoming Resistance to EGFR-TKIs Therapy in EGFR-Mutant NSCLC
DOI: 10.12677/acm.2026.161262, PDF,   
作者: 苗 霂：承德医学院研究生院，河北 承德；刘 峥*：邯郸市中心医院肿瘤三科，河北 邯郸
关键词: 非小细胞肺癌；EGFR-TKIs；耐药机制；个体化治疗；联合治疗；Non-Small Cell Lung Cancer； EGFR-TKIs； Resistance Mechanisms； Personalized Therapy； Combination Therapy
摘要: 非小细胞肺癌(non-small cell lung cancer, NSCLC)是全球范围内发病率和死亡率最高的恶性肿瘤之一，其中表皮生长因子受体(epidermal growth factor receptor, EGFR)突变是NSCLC最重要的分子标志物之一。EGFR酪氨酸激酶抑制剂(EGFR-TKIs)已成为EGFR突变晚期NSCLC患者的标准治疗方案，并极大地改善了患者的生存预后。然而，尽管一线EGFR-TKIs治疗可取得较好的初始疗效，但几乎所有患者最终都会发生耐药并导致疾病进展。耐药机制包括EGFR基因二次突变(如T790M、C797S)、旁路通路激活(如MET扩增、HER2扩增)、组织学转化(如小细胞肺癌转化)及上皮–间质转化(epithelial-mesenchymal transition, EMT)等。此外，部分患者在初始EGFR-TKIs治疗时即表现出原发耐药。近年来，针对EGFR-TKIs耐药的研究取得了显著进展，包括联合治疗策略、靶向新突变药物以及免疫治疗等新兴疗法的探索。本文综述EGFR-TKIs治疗EGFR突变NSCLC进展的耐药机制、治疗策略及未来发展方向，以期为临床实践提供参考。
Abstract: Non-small cell lung cancer (NSCLC) is one of the most prevalent and lethal malignancies worldwide, with epidermal growth factor receptor (EGFR) mutations being a key molecular biomarker. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have become the standard treatment for patients with advanced EGFR-mutant NSCLC, significantly improving survival outcomes. However, despite the initial efficacy of first-line EGFR-TKIs therapy, nearly all patients eventually develop resistance, leading to disease progression. Resistance mechanisms include secondary EGFR mutations (e.g., T790M, C797S), activation of bypass pathways (e.g., MET amplification, HER2 amplification), histological transformation (e.g., small cell lung cancer transformation), and epithelial-mesenchymal transition (EMT). Additionally, some patients exhibit primary resistance to EGFR-TKIs at treatment initiation. In recent years, significant advances have been made in overcoming EGFR-TKIs resistance, including combination therapy strategies, targeted agents against emerging mutations, and novel immunotherapeutic approaches. This review summarizes the resistance mechanisms, therapeutic strategies, and future directions of EGFR-TKIs treatment in EGFR-mutant NSCLC, aiming to provide insights for clinical practice.
文章引用：苗霂, 刘峥. EGFR-TKIs治疗EGFR突变耐药NSCLC的治疗策略[J]. 临床医学进展, 2026, 16(1): 2072-2079. https://doi.org/10.12677/acm.2026.161262

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