Such approaches have begun to be investigated in preclinical and clinical trials, and co-inhibition of RAS-MAPK-ERK and PI3K-AKT-mTOR signaling has demonstrated antitumor effects in the HNSCC PDX model [56] and the PIK3CA+ OSCC preclinical model [57]. This evidence concerns the gene PIK3CA and head and neck squamous cell carcinoma.