克服致癌基因驱动的非小细胞肺癌中MET介导的耐药性。
Overcoming MET-mediated resistance in oncogene-driven NSCLC.
作者信息
Reischmann Nadine, Schmelas Carolin, Molina-Vila Miguel Ángel, Jordana-Ariza Núria, Kuntze Daniel, García-Roman Silvia, Simard Manon A, Musch Doreen, Esdar Christina, Albers Joachim, Karachaliou Niki
机构信息
The Healthcare Business of Merck KGaA, Darmstadt, Germany.
Pangaea Oncology, Hospital Universitario Quiron-Dexeus, Barcelona, Spain.
出版信息
iScience. 2023 May 29;26(7):107006. doi: 10.1016/j.isci.2023.107006. eCollection 2023 Jul 21.
This study evaluates the efficacy of combining targeted therapies with MET or SHP2 inhibitors to overcome MET-mediated resistance in different NSCLC subtypes. A prevalence study was conducted for MET amplification and overexpression in samples from patients with NSCLC who relapsed on ALK, ROS1, or RET tyrosine kinase inhibitors. MET-mediated resistance was detected in 37.5% of tissue biopsies, which allow the detection of MET overexpression, compared to 7.4% of liquid biopsies. The development of drug resistance by MET overexpression was confirmed in -, -, -, and -mutant cell lines. The combination of targeted therapy with MET or SHP2 inhibitors was found to overcome MET-mediated resistance in both and assays. This study highlights the importance of considering MET overexpression as a resistance driver to NSCLC targeted therapies to better identify patients who could potentially benefit from combination approaches with MET or SHP2 inhibitors.
本研究评估了将靶向治疗与MET或SHP2抑制剂联合使用以克服不同非小细胞肺癌（NSCLC）亚型中MET介导的耐药性的疗效。对在ALK、ROS1或RET酪氨酸激酶抑制剂治疗后复发的NSCLC患者样本中的MET扩增和过表达进行了一项患病率研究。在37.5%的组织活检中检测到MET介导的耐药性，这些活检能够检测到MET过表达，而液体活检中的这一比例为7.4%。在-、-、-和-突变细胞系中证实了MET过表达导致的耐药性发展。在-和-试验中发现，靶向治疗与MET或SHP2抑制剂联合使用可克服MET介导的耐药性。本研究强调了将MET过表达视为NSCLC靶向治疗耐药驱动因素的重要性，以便更好地识别可能从与MET或SHP2抑制剂联合治疗方法中获益的患者。
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