Moreover, bortezomib could restore TRAIL-mediated apoptosis in MM cell lines, RPMI 8226 and U266, by reducing c-FLIP protein expression concomitantly enhancing DR4 and DR5 expression (95) in HPV-positive head and neck cancer (HNC) cells by ameliorating activation of caspase-8, -9, and -3, improving membrane expression of DR5, cytochrome c release, and inducing G2/M arrest (96), and also in HCC cells by inhibition of the PI3K/Akt pathway (97). This evidence concerns the gene TNFSF10 and hepatocellular carcinoma.