While significant advancements have been made in the available therapies for metastatic non-small cell lung cancer (NSCLC), acquired resistance remains a major barrier to treatment. We have not yet achieved the ability to cure advanced NSCLC with systemic therapy, despite our growing understanding of many of the oncogenic drivers of this disease. Rather, the emergence of drug-tolerant and drug-resistant cells remains the rule, even in the face of increasingly potent targeted therapies. In this review, we provide a broad overview of the mechanisms of resistance to targeted therapy that have been demonstrated across molecular subtypes of NSCLC, highlighting the dynamic interplay between driver oncogene, bypass signaling pathways, shifting cellular phenotypes, and surrounding tumor microenvironment.

中文翻译：

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NSCLC 靶向治疗的获得性耐药：更新和不断发展的见解。

虽然转移性非小细胞肺癌 (NSCLC) 的可用疗法取得了重大进展，但获得性耐药仍然是治疗的主要障碍。尽管我们越来越了解这种疾病的许多致癌驱动因素，但我们还没有实现通过全身治疗治愈晚期 NSCLC 的能力。相反，即使面对越来越有效的靶向治疗，耐药细胞和耐药细胞的出现仍然是常态。在这篇综述中，我们广泛概述了已在 NSCLC 分子亚型中证明的靶向治疗耐药机制，强调了驱动癌基因、旁路信号通路、转变细胞表型和周围肿瘤微环境之间的动态相互作用。