C-Met as a potential target for the treatment of gastrointestinal cancer: Current status and future perspectives.
Afsane BahramiSoodabeh ShahidsalesMajid KhazaeiMajid Ghayour-MobarhanMina MaftouhSeyed Mahdi HassanianSoodabeh ShahidsalesPublished in: Journal of cellular physiology (2017)
Aberrant activation of the HGF/c-Met signalling pathways is shown to be related with cell proliferation, progression, metastasis, and worse prognosis in several tumor types, including gastrointestinal cancers, suggesting its value as a stimulating-target for cancer-therapy. Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement. The main aim of current review is to give an overview on the role of c-Met/HGF pathway in gastrointestinal cancer, in preclinical and clinical trials. Although several important matters is still remained to be elucidated on the molecular pathways underlying the antitumor effects of this therapy in gastrointestinal-cancers. Further investigations are warranted to recognize the main determinants of the activity of c-Met inhibitors, for parallel targeting signalling pathway associated/activated via MET/HGF pathway or in response to the cell resistance to anti-c-Met agents. Additionally, identification of patients that might benefit from therapy could help to increase the selectivity and efficacy of the therapy.
Keyphrases
- tyrosine kinase
- cancer therapy
- clinical trial
- cell proliferation
- end stage renal disease
- chronic kidney disease
- drug delivery
- papillary thyroid
- newly diagnosed
- ejection fraction
- epidermal growth factor receptor
- single molecule
- mesenchymal stem cells
- peritoneal dialysis
- climate change
- prognostic factors
- phase ii
- double blind