Taking early preventive interventions to manage the challenging issue of acquired resistance to third-generation EGFR inhibitors.
Taking early preventive interventions to manage the challenging issue of acquired resistance to third-generation EGFR inhibitors.
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DOI：
10.1016/j.pccm.2022.10.001
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发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Sun, Shi-Yong
中科院分区：
文献类型：
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作者：
Sun, Shi-Yong
尽管奥希替尼等第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗EGFR激活突变的非小细胞肺癌（NSCLC）的临床疗效令人鼓舞，但无论作为一线还是二线治疗，都不可避免地会出现药物获得性耐药。因此，管理第三代 EGFR-TKI 的获得性耐药对于临床改善患者生存至关重要。人们付出了巨大的努力来开发潜在有效的策略或方案来治疗 EGFR 突变 NSCLC 患者在接受这些 TKI 治疗后复发后，希望患者能够通过克服获得性耐药继续从治疗中受益。尽管这种旨在克服药物获得性耐药性的方法是必要且重要的，但它是一种被动的做法。在疾病进展之前尽早采取预防措施来控制不可避免的获得性耐药的发展提供了同样重要和有效的方法。我们坚信，使用有效且可耐受的联合方案进行早期预防干预，干扰获得性耐药的形成过程，可能会显着改善第三代 EGFR-TKI 治疗 EGFR 突变 NSCLC 的结果。因此，本综述重点讨论延迟甚至预防第三代 EGFR-TKI（特别是奥希替尼）获得性耐药出现的科学原理和机制驱动策略。
Although the clinical efficacies of third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as osimertinib in the treatment of non-small cell lung cancer (NSCLC) with EGFR-activating mutations are promising, drug-acquired resistance inevitably occurs whether they are used as first-line or second-line treatment. Therefore, managing the acquired resistance to third-generation EGFR-TKIs is crucial in the clinic for improving patient survival. Great efforts have been made to develop potentially effective strategies or regimens for the treatment of EGFR-mutant NSCLC patients after relapse following these TKIs therapies with the hope that patients will continue to benefit from treatment through overcoming acquired resistance. Although this approach, which aims to overcome drug-acquired resistance, is necessary and important, it is a passive practice. Taking preventive action early before disease progression to manage the unavoidable development of acquired resistance offers an equally important and efficient approach. We strongly believe that early preventive interventions using effective and tolerable combination regimens that interfere with the process of developing acquired resistance may substantially improve the outcomes of EGFR-mutant NSCLC treatment with third-generation EGFR-TKIs. Thus, this review focuses on discussing the scientific rationale and mechanism-driven strategies for delaying and even preventing the emergence of acquired resistance to third-generation EGFR-TKIs, particularly osimertinib.