Since the alteration of p63 in HNSCC is a documented event, the serine de novo biosynthesis and the OCM alteration, which can be under the regulation of p63 itself in HNSCC should be better evaluated, representing a potential therapeutical target since many compounds are rapidly being made available for modulating the activity of the enzymes of these two metabolisms (e.g. PHGDH inhibitors, SHMT2 inhibitors) and the influence of metabolism on sensitivity to therapy has been demonstrated in various tumoral contexts [63, 78–80]. Here, SHMT2 is linked to head and neck squamous cell carcinoma.