19 General introduction in adequate and well described patient cohorts (81). It should be stressed that the reported mutations and copy number alterations concern all sites of the head and neck region and not OSCC specifically since the number of OSCC specific studies are too low (81). In the majority of cancers including HNSCCs, activation of MET occurs in already transformed cells to increase their proliferative, anti-apoptotic, and migratory potential. In this context, MET is transcriptionally activated by stimuli such as hypoxia, inflammatory cytokines, stromal HGF, and pro-angiogenic factors, often abundantly present in the reactive tumor-associated stroma (71). Notwithstanding that MET expression is associated with poor prognosis in various solid cancers (85)—among which HNSCCs (86)—and numerous targeted therapies are subjective to investigation (72, 87), major survival benefits have not yet been obtained (87, 88). This, together with the fact that the average price of cancer drugs reach approximately $100,000 per year of treatment per patient, hinders the use of MET inhibitors in clinical practice (89, 90). This raises questions as: who to treat or better how to select? 1
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