Multiple myeloma is an incurable blood cancer, but recent studies are beginning to delineate the circuits inside MM cells regulating growth, survival and response to chemotherapy. Most chemotherapy modalities kill tumor cells by triggering cell-death circuits, and defects in this network results in the development of drug-resistance. In this study, I will test combinations of anti-MM agents to prevent occurrence of drug resistance, promote tumor cell killing, reduce attendant toxicity and improve patient outcome.