Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma are a frequent class of driver mutations. Single EGFR tyrosine kinase inhibitor (TKI) provides substantial clinical benefit, but almost nil radiographic complete responses. Patients invariably progress, although survival can reach several years with post-treatment therapies, including EGFR TKIs, chemotherapy or other procedures. Endeavours have been clinically oriented to manage the acquisition of EGFR TKI-resistant mutations; however, basic principles on cancer evolution have not been considered in clinical trials. For years, evidence has displayed rapidly adaptive mechanisms of resistance to selective monotherapy, posing several dilemmas for the practitioner. Strict adherence to non-small cell lung cancer (NSCLC) guidelines is not always practical for addressing the clinical progression that EGFR-mutant lung adenocarcinoma patients suffer. The purpose of this review is to highlight regulatory mechanisms and signalling pathways that cause therapy-induced resistance to EGFR TKIs. It suggests combinatorial therapies that target EGFR, as well as potential mechanisms underlying EGFR-mutant NSCLC, alerting the reader to clinical opportunities that may lead to a deeper and more durable response. Molecular reprogramming contributes to EGFR TKI resistance, and the compiled information is relevant in understanding the development of new combined targeted strategies in EGFR-mutant NSCLC.

肺腺癌中的表皮生长因子受体 (EGFR) 突变是一类常见的驱动突变。单一的 EGFR 酪氨酸激酶抑制剂 (TKI) 提供了显着的临床益处，但几乎没有放射学完全反应。患者总是会进步，尽管通过包括 EGFR TKI、化学疗法或其他程序在内的治疗后治疗，存活率可以达到数年。努力以临床为导向来管理 EGFR TKI 抗性突变的获得；然而，在临床试验中并未考虑癌症进化的基本原理。多年来，证据已经显示出对选择性单一疗法的快速适应性机制，给从业者带来了几个困境。严格遵守非小细胞肺癌 (NSCLC) 指南对于解决 EGFR 突变肺腺癌患者遭受的临床进展并不总是切实可行的。本综述的目的是强调导致治疗诱导的对 EGFR TKI 耐药的调节机制和信号通路。它提出了针对 EGFR 的组合疗法，以及 EGFR 突变 NSCLC 的潜在机制，提醒读者注意可能导致更深入和更持久反应的临床机会。分子重编程有助于 EGFR TKI 耐药性，并且汇编的信息与了解 EGFR 突变 NSCLC 中新的联合靶向策略的发展相关。本综述的目的是强调导致治疗诱导的对 EGFR TKI 耐药的调节机制和信号通路。它提出了针对 EGFR 的组合疗法，以及 EGFR 突变 NSCLC 的潜在机制，提醒读者注意可能导致更深入和更持久反应的临床机会。分子重编程有助于 EGFR TKI 耐药性，并且汇编的信息与了解 EGFR 突变 NSCLC 中新的联合靶向策略的发展相关。本综述的目的是强调导致治疗诱导的对 EGFR TKI 耐药的调节机制和信号通路。它提出了针对 EGFR 的组合疗法，以及 EGFR 突变 NSCLC 的潜在机制，提醒读者注意可能导致更深入和更持久反应的临床机会。分子重编程有助于 EGFR TKI 耐药性，并且汇编的信息与了解 EGFR 突变 NSCLC 中新的联合靶向策略的发展相关。