The increase in phosphorylated 4EBP1 downstream of the PIK3-AKT-mTOR signaling is an important modification that supports eIF4F formation, and inhibitors of mTOR such as rapamycin and its synthetic analogs that increase dephosphorylated levels of 4EBP1 showed promise in the treatment of HNSCC as short-term monotherapy prior to definitive treatment [33]. This evidence concerns the gene EIF4EBP1 and head and neck squamous cell carcinoma.