Zaanan Aziz, Laurent-Puig Pierre, Taieb Julien
Hôpital européen Georges-Pompidou, AP-HP, Service de gastroentérologie et oncologie digestive, 20, rue Leblanc, 75015 Paris, France, UMR-S775, Inserm, Paris, France.
UMR-S775, Inserm, Paris, France.
Bull Cancer. 2014 Jan 1;101(1):25-30. doi: 10.1684/bdc.2013.1870.
The MET receptor tyrosine kinase and its ligand HGF regulates many signalling pathways involved in proliferation and cell motility, invasion and angiogenesis. Deregulation of HGF-MET system by different biological mechanisms may contribute to the tumour development in many types of cancers. Some pharmacological approaches have been developed to inhibit the HGF-MET signalling pathway, using monoclonal antibodies against HGF or MET, or using tyrosine kinase inhibitors of MET receptor. In digestive cancers, several clinical studies have evaluated the safety and efficacy of these targeted therapies, with some promising results but requiring confirmation in phase III trials. Moreover, it appears that MET tumour expression could be a predictive marker of response to these targeted therapies for some gastrointestinal tumours. Thus, somatic alterations in HGF-MET system may represent interesting therapeutic targets and help to select patients who can favourably respond to such targeted treatment.
MET受体酪氨酸激酶及其配体HGF调节许多参与增殖、细胞运动、侵袭和血管生成的信号通路。通过不同生物学机制使HGF-MET系统失调可能会促进多种癌症的肿瘤发展。已经开发了一些药理学方法来抑制HGF-MET信号通路，使用针对HGF或MET的单克隆抗体，或使用MET受体的酪氨酸激酶抑制剂。在消化系统癌症中，多项临床研究评估了这些靶向治疗的安全性和有效性，取得了一些有前景的结果，但需要在III期试验中得到证实。此外，MET肿瘤表达似乎可能是某些胃肠道肿瘤对这些靶向治疗反应的预测标志物。因此，HGF-MET系统中的体细胞改变可能代表了有趣的治疗靶点，并有助于选择可能对这种靶向治疗产生良好反应的患者。
