Department of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, Amsterdam, the Netherlands; Fondazione Pisana per la Scienza, Pisa, Italy.
Department of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, Amsterdam, the Netherlands.
Crit Rev Oncol Hematol. 2021 Oct;166:103454. doi: 10.1016/j.critrevonc.2021.103454. Epub 2021 Aug 26.
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-TKIs）已被开发用于治疗携带 EGFR 激活突变的晚期/转移性非小细胞肺癌（NSCLC）患者，而第四代正在进行临床前评估。尽管最初有效，但由于出现了携带多种耐药机制的克隆，EGFR-TKIs 的获得性耐药通常在一年内发生。因此，EGFR-TKIs 与其他治疗药物的联合已成为克服耐药性和改善临床结果的潜在策略。然而，迄今为止的结果并不明确，对于在 EGFR-TKIs 治疗期间发生疾病进展的患者，理想的治疗方法仍难以捉摸。本文综述了 EGFR-TKIs 的最新进展，并描述了导致这些药物耐药的机制。此外，还讨论了目前关于 EGFR-TKIs 与其他抗癌药物联合应用的知识、局限性和未来展望，支持在选定人群中采用从基础到临床的方法。
