Research progress on the mechanism of resistance to MET inhibitors in non-small cell lung cancer and review of MET inhibitor resistance-related strategies
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摘要: MET基因是非小细胞肺癌的重要肿瘤驱动基因，针对MET 14外显子跳跃突变的靶向药物为患者带来新的治疗希望。虽然以tepotinib和沃利替尼等为代表的MET抑制剂显示出良好的抗肿瘤效果，但MET抑制剂的耐药不可避免。通过对HGF/MET信号通路的研究，不仅有助于探索MET抑制剂的耐药机制，有利于找到抑制和逆转耐药的方法，而且能够扩大新药研发的领域。初步研究显示HGF/MET信号通路抑制剂与其他药物的联合应用可能具有更大的临床应用潜力。本文就MET基因异常的特点，MET抑制剂的耐药机制和应对耐药策略进行综述，并提出MET抑制剂未来的发展方向和面临的挑战。Abstract: The MET gene is an important tumor-driving gene for non-small cell lung cancer (NSCLC). Drugs targeting tumor with MET exon 14 skipping mutations bring new hope for patients. Although MET inhibitors such as tepotinib and savolitinib have shown good antitumor effects, resistance is inevitable. Studies on the hepatocyte growth factor (HGF)/mesenchymal- epithelial transition factor (MET) signaling pathway will not only help explore the mechanism underlying resistance to MET inhibitors, they may aid in the discovery of strategies for inhibiting and reversing drug resistance, thereby expanding the field of novel drug development. Preliminary studies have shown that the combination of HGF/MET inhibitors with other drugs may have great potential for clinical applications. This article reviews the characteristics of MET gene abnormalities, the mechanism of resistance against MET inhibitors, and the strategies for responding to resistance. Finally, the challenges posed by MET inhibitors is discussed and guidance on the direction of future development of MET inhibitors is proposed.
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