Three generations of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs) have been developed for treating advanced/metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations, while a fourth generation is undergoing preclinical assessment. Although initially effective, acquired resistance to EGFR-TKIs usually arises within a year due to the emergence of clones harboring multiple resistance mechanisms. Therefore, the combination of EGFR-TKIs with other therapeutic agents has emerged as a potential strategy to overcome resistance and improve clinical outcomes. However, results obtained so far are ambiguous and ideal therapies for patients who experience disease progression during treatment with EGFR-TKIs remain elusive.

This review provides an updated landscape of EGFR-TKIs, along with a description of the mechanisms causing resistance to these drugs. Moreover, it discusses the current knowledge, limitations, and future perspective regarding the use of EGFR-TKIs in combination with other anticancer agents, supporting the need for bench-to-bedside approaches in selected populations.

三代表皮生长因子受体酪氨酸激酶抑制剂 (EGFR-TKI) 已开发用于治疗携带EGFR激活突变的晚期/转移性非小细胞肺癌 (NSCLC) 患者，而第四代正在接受临床前评估。尽管最初有效，但由于具有多种耐药机制的克隆的出现，EGFR-TKIs 获得性耐药通常会在一年内出现。因此，EGFR-TKI 与其他治疗药物的组合已成为克服耐药性和改善临床结果的潜在策略。然而，对于在 EGFR-TKIs 治疗期间出现疾病进展的患者而言，迄今为止获得的结果尚不明确，理想的治疗方法仍然难以捉摸。

本综述提供了 EGFR-TKI 的最新情况，并描述了导致对这些药物产生耐药性的机制。此外，它还讨论了关于 EGFR-TKIs 与其他抗癌药物联合使用的当前知识、局限性和未来前景，支持在选定人群中采用从工作台到床边方法的必要性。