Su Qilong, Hou Jingyu, Du Xinhui, Zhang Fan, Zhang Panhong, Wang Bangmin, Yao Weitao
The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Oncol Rev. 2025 Jun 17;19:1615111. doi: 10.3389/or.2025.1615111. eCollection 2025.
MET, a receptor tyrosine kinase proto-oncogene and the specific receptor for hepatocyte growth factor (HGF), plays a critical role in the initiation and progression of osteosarcoma (OS) through sustained pathway activation. Aberrant activation of MET has been shown to trigger multiple downstream signalling pathways, including RAS-ERK, PI3K-AKT, and STAT3, which are essential for OS cell proliferation, invasion, differentiation, and drug resistance. In recent years, significant progress has been made in the development of small-molecule inhibitors and specific antibodies targeting MET for OS therapy. The use of combination therapy as a treatment strategy involves the use of MET inhibitors in conjunction with chemotherapy, immunotherapy, and other targeted therapies. This approach has the potential to overcome resistance and improve therapeutic efficacy. This review summarises the mechanisms of MET signalling in OS, with a focus on the progress of MET-targeted therapies and their combination with other therapeutic strategies. The study provides valuable insights into future research directions, offering novel perspectives on the role of MET as a therapeutic target in OS.
MET是一种受体酪氨酸激酶原癌基因，也是肝细胞生长因子（HGF）的特异性受体，通过持续的信号通路激活在骨肉瘤（OS）的发生和发展中起关键作用。MET的异常激活已被证明会触发多个下游信号通路，包括RAS-ERK、PI3K-AKT和STAT3，这些通路对OS细胞的增殖、侵袭、分化和耐药性至关重要。近年来，在开发针对OS治疗的MET小分子抑制剂和特异性抗体方面取得了重大进展。联合治疗作为一种治疗策略，涉及将MET抑制剂与化疗、免疫治疗和其他靶向治疗联合使用。这种方法有可能克服耐药性并提高治疗效果。本综述总结了OS中MET信号传导的机制，重点关注MET靶向治疗及其与其他治疗策略联合使用的进展。该研究为未来的研究方向提供了有价值的见解，为MET作为OS治疗靶点的作用提供了新的视角。
