Bortezomib blocks the degradation of IκBα, an inhibitory protein that is constitutively bound to cytosolic NF-κB, thereby inhibiting the nuclear translocation and activation of NF-κB. Bortezomib induces apoptosis by activating caspase-8 and caspase-9 in drug-resistant MM cell lines and primary cancer cells derived from MM patients. This evidence concerns the gene CASP8 and Miyoshi myopathy.