Multiple myeloma is a fatal disease requiring new treatment approaches. It has recently been found that combining a disruptor of the cell cycle (UCN-01) with pharmacologic inhibitors of a key survival pathway (MAPK) dramatically induces cell death (apoptosis) in human myeloma cells. This project aims to identify the mechanism underlying this phenomenon, and to extend these findings to include primary cells obtained from patients with multiple myeloma. The ultimate goal is to develop a novel chemotherapeutic strategy combining UCN-01 and MAPK inhibitors, both of which are currently in clinical trials in humans, for the treatment of patients with multiple myeloma.