PIK3CA and head and neck squamous cell carcinoma: This can be explained by the fact that PIK3CA wild type HNSCC cells (Cal27, HN12, and SCC47) ectopically expressing mutant PIK3CA have higher levels of basal AKT and mTOR activation, therefore becoming insensitive to HER3 blockade, similar to that of Detroit 562 cells, a PIK3CA + HNSCC cell line harboring PIK3CA H1047R mutations endogenously (Fig. 3c and Supplementary Fig. 5).