EGFR and head and neck squamous cell carcinoma: In the present study, we show (i) a higher rate of gene mutations with putative protein-changing characteristics in non-responders to β1 integrin and EGFR targeting, (ii) mutational profiles of responders and non-responders that allow stratification of HNSCC patients, and (iii) pharmacological inhibition of KEAP1 and mTOR to effectively diminish non-responder insusceptibility to β1 integrin and EGFR targeting for radiosensitization.