220 Chapter 7 and MET-EC- may represent useful and complementing biomarkers in the identification of OSCC patients that might benefit from MET-targeted therapies in the first line setting. To this aim, it would be recommended to use MET moAbs or tyrosine kinase inhibitors (TKIs) for cancers positive for the full-length receptor, and TKIs or a combination of both for MET-EC- cancers (42, 47) (Figure 3). Figure 3: Recommended use of MET-targeted therapies, moAbs and/or TKIs, in OSCC based on the receptor’s post-translational status on the membrane. Use of MET moAbs directed against the N-term extracellular and C-terminal intracellular domain stratifies OSCCs into three categories: MET negative (no MET immunoreactivity), decoy MET (more positivity for the N-terminal moAb), and transmembranous C-terminal MET (equal positivity for both moAbs (complete MET) or more positivity for the C-terminal moAb (complete MET and/or MET-EC-). As patients falling in the third category develop cancers that are positive for the protein’s catalytic domain, they are presumably eligible for treatment with MET-targeted therapies. The use of MET moAbs, or TKIs is recommended in case of complete MET. The use of TKIs, or a combination of TKI and moAbs is recommended in case of complete MET and/or MET-EC-. This figure and its legend was inspired on Figure 10 and its legend by De Herdt et al. (42). Discussion Experiments using immortalized cell lines and patient-derived xenografts have illustrated that tumors harboring MET mutations and amplifications are responsive to MET blockade in the form of cell cycle arrest and/or apoptosis in vitro (54)
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