These findings suggest that heterodimers of EGFR/HER3 and HER2/HER3 promote HER3 phosphorylation, and the consequent activation of PI3K/AKT/mTOR activity by the assembly of HER3-PI3K molecular complexes, thus representing a key signaling hub in HNSCC (scheme in Fig. 2e). This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.