Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Int J Mol Sci. 2024 Aug 22;25(16):9101. doi: 10.3390/ijms25169101.
Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal-epithelial transition factor (c-MET). Among these, the hepatocyte growth factor (HGF)/c-MET signaling pathway plays a crucial role in NSCLC. In spite of this, the involvement of the HGF/c-MET signaling axis in remodeling the tumor microenvironment (TME) remains relatively unexplored. This review explores the biological functions of the HGF/c-MET signaling pathway in both normal and cancerous cells, examining its multifaceted roles in the NSCLC tumor microenvironment, including tumor cell proliferation, migration and invasion, angiogenesis, and immune evasion. Furthermore, we summarize the current progress and clinical applications of MET-targeted therapies in NSCLC and discuss future research directions, such as the development of novel MET inhibitors and the potential of combination immunotherapy.
非小细胞肺癌(NSCLC)的特征是存在几种分子改变,这些改变促进了其发生和发展。这些改变包括表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)、人表皮生长因子受体 2(HER2)和间质-上皮转化因子(c-MET)。在这些改变中,肝细胞生长因子(HGF)/c-MET 信号通路在 NSCLC 中起着至关重要的作用。尽管如此,HGF/c-MET 信号轴在重塑肿瘤微环境(TME)中的作用仍相对未被探索。本综述探讨了 HGF/c-MET 信号通路在正常和癌细胞中的生物学功能,研究了其在 NSCLC 肿瘤微环境中的多方面作用,包括肿瘤细胞增殖、迁移和侵袭、血管生成和免疫逃逸。此外,我们总结了 MET 靶向治疗在 NSCLC 中的最新进展和临床应用,并讨论了未来的研究方向,如新型 MET 抑制剂的开发和联合免疫治疗的潜力。