The 26S proteasome is a promising new target for breast cancer therapy. The 
degradation of proteins by the proteasome is an essential metabolic process, and 
inhibition of the proteasome results in cell-cycle arrest and apoptosis. 
However, cancer cells and proliferating blood vessels appear to be particularly 
sensitive to the effects of proteasome inhibition. Studies carried out in breast 
cancer cells and murine xenograft models of breast cancer have demonstrated the 
potent antitumor effects of proteasome inhibition in this disease. Proteasome 
inhibition interferes with many cell signaling pathways, including those 
involved in the development and progression of breast cancer. The potent and 
selective proteasome inhibitor bortezomib (VELCADE; formerly known as PS-341) is 
particularly promising as a potential anticancer agent. PS-341 is the first 
proteasome inhibitor to be extensively studied in murine models of cancer and to 
progress to clinical trials in cancer patients. Preliminary clinical data from 
patients with a range of malignancies indicate that the drug effectively 
inhibits proteasome activity at doses associated with manageable toxicity. Early 
clinical trials are currently recruiting participants for the analysis of PS-341 
activity in breast cancer.