Clinical Medicine Reviews in Oncology

Multiple Myeloma is the second leading hematologic cancer in the United States with approximately 20,000 new cases diagnosed each year. Although myeloma remains incurable, significant progress has been made in developing new therapeutics resulting in improved overall survival. In the last ten years, the average survival of patients with advanced myeloma has almost doubled. Much of this success can be attributed to the development and clinical use of the first-in-class proteasome inhibitor bortezomib. The proteasome is a multicatalytic proteinase complex essential for protein metabolism and regulation of cellular homeostasis. Through inhibition of proteasome function, bortezomib has demonstrated significant anti-myeloma responses in both pre-clinical models and in human studies. Bortezomib is now approved for use in patients with newly diagnosed and refractory myeloma, and in combination with other chemotherapeutic agents. This review will discuss the pre-clinical studies evaluating the mechanism of action of proteasome inhibition, outline the clinical development of bortezomib as treatment for patients with newly diagnosed and relapsed multiple myeloma and describe the safety of bortezomib in human studies. Several second generation proteasome inhibitors are now showing promise in early phase clinical trials, foreshadowing a new era of targeted therapy for multiple myeloma.