IGF1 and Miyoshi myopathy: Other mechanisms of resistance that have been observed in MM cell lines and disease models include up-regulation of heat-shock proteins (such as HSP90 and HSP27) which function as ubiquitin chaperones, which may facilitate NF-κB signaling, increased efflux transporter P-gp expression (which lowers intracellular bortezomib concentrations), up-regulation of proteasome subunits and increased basal proteasome activity, upregulation in Il-6, IGF-1 and other cytokines in the MM microenvironment, and increased growth signaling through insulin-like growth factor (IGF) and other pathways [27,28].