In malignant glioma cells, both drugs were shown to cause cell death through stimulation of ER stress response, indicated by increased expression of GRP78 and CHOP and activation of ER stress response-associated caspase-4.60 Combination of bortezomib, a proteasome inhibitor, with ritonavir demonstrated enhanced anticancer activity in sarcoma cells, resulting in > 90% apoptosis.61 This combination strongly increased the level of ER stress and activated PERK, IRE1, and ATF6, in addition to synergistically inducing CHOP, JNK, caspase-4, and caspase-9, causing irreversible stress and cell death. This evidence concerns the gene CASP4 and malignant glioma.