表皮生长因子受体（EGFR）突变是非小细胞肺癌（NSCLC）最常见的致癌驱动因素。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）被广泛应用于肺癌治疗，特别是在晚期NSCLC的一线治疗中，与标准化化疗相比，EGFR-TKI单药治疗取得了更好的疗效和耐受性。然而，EGFR-TKI获得性耐药和相关不良事件是针对性肺癌治疗的重要障碍。因此，迫切需要寻求有效的干预措施来克服这些限制。天然药物在逆转EGFR-TKI获得性耐药和减少不良反应方面展现了潜在的治疗优势，为EGFR-TKI联合疗法带来了新的选择和方向。在本文中，我们系统地阐述了EGFR-TKI的耐药机制、每一代EGFR-TKI在NSCLC协同治疗中的临床策略、EGFR-TKI的治疗相关不良事件以及传统中药在克服EGFR-TKI的耐药和不良反应方面的潜在作用。草药和活性成分具有通过多条途径和整体调节的多种机制协同作用，联合靶向治疗，有望成为NSCLC治疗的创新模式。版权所有©2023 Song、Cao、Ni、Wang、Qin、Sun、Xu、Wang和Li。

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used in the treatment of lung cancer, especially in the first-line treatment of advanced NSCLC, and EGFR-TKIs monotherapy has achieved better efficacy and tolerability compared with standard chemotherapy. However, acquired resistance to EGFR-TKIs and associated adverse events pose a significant obstacle to targeted lung cancer therapy. Therefore, there is an urgent need to seek effective interventions to overcome these limitations. Natural medicines have shown potential therapeutic advantages in reversing acquired resistance to EGFR-TKIs and reducing adverse events, bringing new options and directions for EGFR-TKIs combination therapy. In this paper, we systematically demonstrated the resistance mechanism of EGFR-TKIs, the clinical strategy of each generation of EGFR-TKIs in the synergistic treatment of NSCLC, the treatment-related adverse events of EGFR-TKIs, and the potential role of traditional Chinese medicine in overcoming the resistance and adverse reactions of EGFR-TKIs. Herbs and active compounds have the potential to act synergistically through multiple pathways and multiple mechanisms of overall regulation, combined with targeted therapy, and are expected to be an innovative model for NSCLC treatment.Copyright © 2023 Song, Cao, Ni, Wang, Qin, Sun, Xu, Wang and Li.