Proteasome inhibitors in cancer therapy

Inhibitors of the proteasome have long been used in studies of protein turnover, but in a notable example of successful translational research they have made the leap from the laboratory into the clinical arena. The proteasome inhibitor bortezomib (VELCADE, formerly known as PS-341), has recently been approved in the United States for treatment of patients with multiple myeloma who have received at least two prior therapies, and have demonstrated disease progression on their last therapy. Furthermore, studies of this agent in other hematologic malignancies and solid tumors are underway, and other proteasome inhibitors for clinical use are under development as well. This chapter provides the reader with guidelines for the optimal clinical administration of VELCADE for its currently approved indication, as well as some suggestions for subsequent management of treatment-related events in these patients.