Additional promising pre-clinical work has explored Second Mitochondria-derived Activator of Caspases (SMAC)-mimetics, antagonists of inhibitors of apoptosis, which seem particularly effective against HNSCC models with FADD/BIRC2 alterations [165, 166]; particularly meaningful considering the aforementioned high incident of FADD/BIRC2 alterations in HNSCC (Table 1). Here, BIRC2 is linked to head and neck squamous cell carcinoma.