A model of circumvention of bortezomib resistance in bortezomib-resistant multiple myeloma cells by the MUC1 inhibitor GO-203. In this model, resistant cells exhibit an amplified antioxidant response to bortezomib, manifested by upregulation of the glycolytic pathway-regulating protein TIGAR, leading to marked GSH accumulation. The latter sharply reduces the accumulation of toxic ROS species, thereby attenuating cell death. GO-203 effectively blocks TIGAR upregulation and GSH accumulation in bortezomib-treated cells, substantially increasing toxic ROS generation, culminating in the synergistic induction of cells death. Not shown is the induction of ER stress and CHOP upregulation by enhanced oxidative injury in bortezomib-sensitive cells (but not in resistant cells), which may contribute to cell death in the former.