Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 432, Houston, TX 77030-4009, USA.
J Clin Oncol. 2012 Sep 10;30(26):3287-96. doi: 10.1200/JCO.2011.40.3774. Epub 2012 Aug 6.
The hepatocyte growth factor (HGF) and its receptor, the transmembrane tyrosine kinase cMET, promote cell proliferation, survival, motility, and invasion as well as morphogenic changes that stimulate tissue repair and regeneration in normal cells but can be co-opted during tumor growth. MET overexpression, with or without gene amplification, has been reported in a variety of human cancers, including breast, lung, and GI malignancies. Furthermore, high levels of HGF and/or cMET correlate with poor prognosis in several tumor types, including breast, ovarian, cervical, gastric, head and neck, and non-small-cell lung cancers. Gene amplification and protein overexpression of cMET drive resistance to epidermal growth factor receptor family inhibitors, both in preclinical models and in patients. It is increasingly apparent that the HGF-cMET axis signaling network is complex, and rational combinatorial therapy is needed for optimal clinical efficacy. Better understanding of HGF-cMET axis signaling and the mechanism of action of HGF-cMET inhibitors, along with the identification of biomarkers of response and resistance, will lead to more effective targeting of this pathway for cancer therapy.
肝细胞生长因子（HGF）及其受体，跨膜酪氨酸激酶 cMET，可促进细胞增殖、存活、迁移和侵袭，以及刺激组织修复和再生的形态发生变化，但在肿瘤生长过程中可被招募。MET 的过表达，无论是否有基因扩增，已在多种人类癌症中报道，包括乳腺癌、肺癌和胃肠道恶性肿瘤。此外，在多种肿瘤类型中，包括乳腺癌、卵巢癌、宫颈癌、胃癌、头颈部癌和非小细胞肺癌，高水平的 HGF 和/或 cMET 与预后不良相关。cMET 的基因扩增和蛋白过表达导致对表皮生长因子受体家族抑制剂的耐药性，无论是在临床前模型还是在患者中。越来越明显的是，HGF-cMET 轴信号网络很复杂，需要合理的联合治疗才能达到最佳的临床疗效。更好地了解 HGF-cMET 轴信号和 HGF-cMET 抑制剂的作用机制，以及鉴定反应和耐药性的生物标志物，将导致更有效地针对该途径进行癌症治疗。
