Multiple myeloma is a disease that remains incurable. However promising new drugs like Velcade will have an impact. We believe Velcade is active due to a unique feature of myeloma, the secretion of antibodies. The endoplasmic reticulum is where antibodies are made in the cell. When proteins are misfolded in most cells, a series of events called the unfolded protein response (UPR) is activated. However, in myeloma part of the UPR is already active to help make antibodies. We believe that myeloma is sensitive to further ER stress that is caused by Velcade. Experiments are proposed to test this hypothesis.