Despite these limitations, taking all these arguments together and by considering them in the context of previous trials with targeted agents and ongoing trials with immunotherapy as adjuvant or concurrent treatment of HNSCC, the activation of the RAS-signaling pathway has been shown to be responsible of resistance to anti-EGFR agents in recurrent and/or metastatic HNSCC [32]; nevertheless, in the present series, T-with had an intact RAS downstream pathway, therefore being theoretically more sensitive to anti-EGFR drugs. The gene discussed is EGFR; the disease is head and neck squamous cell carcinoma.