These include increased expression of TRAIL-Rs,21,32 enhanced activation of caspase-8,26 stabilisation of BH3-only proteins,19,25 inactivation of XIAP27,34 or induction of p53 or p21.20,27 Based on these studies, we aimed to investigate pathways that contributed to the increased sensitivity of HNSCC cells to TRAIL when combined with bortezomib. The gene discussed is TP53; the disease is head and neck squamous cell carcinoma.