As expected, modulation of Trop2 signaling through the epidermal growth factor receptor 3 (ErbB3), insulin-like growth factor 1 receptor (IGF-1R), and Akt pathways (see Chapter 2.2 and 3.2.6) reflects the observed association between Trop2 expression and resistance to EGFR inhibitor gefinitib in head-and-neck squamous cell carcinoma [148], altered response of Trop2-overexpressing cells to IGF-1R inhibitor AG-1024 in HeLa cells [77], and reduced response of Trop2 shRNA transfected breast cancer cells to allosteric Akt inhibitors [59]. This evidence concerns the gene AKT1 and head and neck squamous cell carcinoma.