Department of Translational Hematology and Oncology Research, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio 44195, USA.
J Thorac Oncol. 2012 Feb;7(2):459-67. doi: 10.1097/JTO.0b013e3182417e44.
MET is a versatile receptor tyrosine kinase within the human kinome which is activated by its specific natural ligand hepatocyte growth factor (HGF). MET signaling plays an important physiologic role in embryogenesis and early development, whereas its deregulation from an otherwise quiescent signaling state in mature adult tissues can lead to upregulated cell proliferation, survival, scattering, motility and migration, angiogenesis, invasion, and metastasis in tumorigenesis and tumor progression. Studies have shown that MET pathway is activated in many solid and hematological malignancies, including lung cancer, and can be altered through ligand or receptor overexpression, genomic amplification, MET mutations, and alternative splicing. The MET signaling pathway is known to be an important novel target for therapeutic intervention in human cancer. A number of novel therapeutic agents that target the MET/HGF pathway have been tested in early-phase clinical studies with promising results. Phase 3 studies of MET targeting agents have just been initiated. We will review the MET signaling pathway and biology in lung cancer and the recent clinical development and advances of MET/HGF targeting agents with emphasis on discussion of issues and strategies needed to optimize the personalized therapy and further clinical development.
MET 是人类激酶组中一种多功能的受体酪氨酸激酶，其可被特定的天然配体肝细胞生长因子（HGF）激活。MET 信号在胚胎发生和早期发育中起着重要的生理作用，而在成熟的成人组织中，其从原本静止的信号状态失调，可能导致细胞增殖、存活、扩散、运动和迁移、血管生成、侵袭和转移等肿瘤发生和肿瘤进展的上调。研究表明，MET 通路在许多实体瘤和血液恶性肿瘤中被激活，包括肺癌，并且可以通过配体或受体过表达、基因组扩增、MET 突变和选择性剪接来改变。MET 信号通路被认为是人类癌症治疗干预的一个重要的新靶点。许多针对 MET/HGF 通路的新型治疗药物已经在早期临床试验中进行了测试，结果令人鼓舞。MET 靶向药物的 3 期研究刚刚开始。我们将回顾肺癌中的 MET 信号通路和生物学，以及最近 MET/HGF 靶向药物的临床进展和进展，重点讨论需要优化个体化治疗和进一步临床开发的问题和策略。
