In a previous study, in HNSCC, we have shown that the contemporary blockade of β2-AR and MEK1/2 has a synergistic effect that boosts cytotoxicity and autophagy and prevents resistance; in fact, β2-AR blockade drives a cell oxidative stress by the inhibition of the nuclear factor erythroid 2-related factor 2 (Nrf2). Here, MAP2K1 is linked to head and neck squamous cell carcinoma.