Wang Kinsley, Hsu Robert
Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA.
Department of Medicine, Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
Antibodies (Basel). 2024 Oct 18;13(4):88. doi: 10.3390/antib13040088.
Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal-epithelial transition () gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor () mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes.
非小细胞肺癌（NSCLC）仍然是全球癌症死亡的主要原因，尽管靶向治疗的进展改善了治疗结果。间充质-上皮转化（MET）基因在NSCLC中起着重要作用，通常通过蛋白质过表达、外显子14跳跃突变和基因扩增，其中许多是作为对其他致癌驱动因素（如表皮生长因子受体（EGFR）突变）的耐药机制出现的。本综述探讨了抗MET抗体疗法的发展和临床疗效。使用主要医学数据库进行了全面的文献检索，查看了关于抗MET抗体研究的关键相关研究。两位作者都对文献进行了综述，评估了研究质量，并解释了每项研究的结果。阿米万他单抗是一种双特异性EGFR/MET抗体，已被批准用于治疗EGFR外显子20插入突变，最近又扩展到用于治疗对奥希替尼耐药的经典EGFR突变。其他正在开发的重要抗MET靶向疗法包括抗体药物偶联物，如替雷利珠单抗维托汀、REGN5093-M114和AZD9592，以及埃米贝妥单抗，它是一种人源化免疫球蛋白G4单克隆二价MET抗体。MET在NSCLC中起着重要作用，阿米万他单抗以及其他抗MET靶向疗法在直接靶向MET和解决对致癌驱动因素的获得性耐药方面发挥着作用。未来的研究应专注于开发新型MET抗体药物，并探索新的治疗组合，以提高NSCLC的治疗效果并克服耐药性。完善生物标志物驱动的方法以确保精确的患者选择对于优化治疗结果也至关重要。
