EGFR and PI3K inhibitor combination has been studied in head and neck squamous cell carcinoma, glioblastoma, ovarian cancer and breast cancer preclinical cell line models, however these studies did not compare the synergistic effects of EGFR amplified and PI3K mutant cells to non-amplified and non-mutant cells [26–34, 36, 37]. Here, PIK3CA is linked to head and neck squamous cell carcinoma.