Qin Kang, Hong Lingzhi, Zhang Jianjun, Le Xiuning
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2023 Jan 18;15(3):612. doi: 10.3390/cancers15030612.
Targeted therapy has emerged as an important pillar for the standard of care in oncogene-driven non-small cell lung cancer (NSCLC), which significantly improved outcomes of patients whose tumors harbor oncogenic driver mutations. However, tumors eventually develop resistance to targeted drugs, and mechanisms of resistance can be diverse. amplification has been proven to be a driver of resistance to tyrosine kinase inhibitor (TKI)-treated advanced NSCLC with its activation of , , , and alterations. The combined therapy of MET-TKIs and EGFR-TKIs has shown outstanding clinical efficacy in -mutated NSCLC with secondary amplification-mediated resistance in a series of clinical trials. In this review, we aimed to clarify the underlying mechanisms of amplification-mediated resistance to tyrosine kinase inhibitors, discuss the ways and challenges in the detection and diagnosis of amplifications in patients with metastatic NSCLC, and summarize the recently published clinical data as well as ongoing trials of new combination strategies to overcome amplification-mediated TKI resistance.
靶向治疗已成为致癌基因驱动的非小细胞肺癌（NSCLC）标准治疗的重要支柱，它显著改善了肿瘤携带致癌驱动基因突变患者的预后。然而，肿瘤最终会对靶向药物产生耐药性，且耐药机制可能多种多样。MET扩增已被证明是酪氨酸激酶抑制剂（TKI）治疗的晚期NSCLC耐药的驱动因素，其通过激活MET、HER2、ERBB3和RAS改变来实现。在一系列临床试验中，MET-TKIs与EGFR-TKIs的联合治疗在具有继发性MET扩增介导耐药的EGFR突变NSCLC中显示出卓越的临床疗效。在本综述中，我们旨在阐明MET扩增介导的酪氨酸激酶抑制剂耐药的潜在机制，讨论转移性NSCLC患者中MET扩增检测与诊断的方法及挑战，并总结最近发表的临床数据以及正在进行的克服MET扩增介导的TKI耐药新联合策略的试验。
