As we found that increased Akt1/2/3 phosphorylation is characteristic for AcqRes HNSCC cell lines and Akt1, Akt2 and Akt3 are expressed in HNSCC patients, we hypothesized that the combination of cetuximab with an Akt inhibitor might be a potential novel therapeutic strategy to overcome acquired cetuximab resistance. This evidence concerns the gene AKT2 and head and neck squamous cell carcinoma.