[MET signalling pathway and its therapeutic implications in gastrointestinal cancers].
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.
Hôpital européen Georges-Pompidou, AP-HP, Service de gastroentérologie et oncologie digestive, 20, rue Leblanc, 75015 Paris, France, UMR-S775, Inserm, Paris, France.
Aziz
A
Zaanan
UMR-S775, Inserm, Paris, France.
Pierre
P
Laurent-Puig
Hôpital européen Georges-Pompidou, AP-HP, Service de gastroentérologie et oncologie digestive, 20, rue Leblanc, 75015 Paris, France.
Julien
J
Taieb
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism
D009363:Neoplasm Proteins; D019859:Proto-Oncogene Proteins c-met
HGF; MET; biomarker; gastrointestinal cancers; targeted therapy