Disappointingly, however, clinical evidence to date shows that EGFR-targeted agents, including monoclonal antibodies and tyrosine kinase inhibitors (TKIs), have little efficacy in HNSCC as a monotherapy, raising the possibility that alternative survival pathways may be activated in this disease (Box et al, 2013a, 2013b). This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.