Mechanism of action and determinants of sensitivity to the proteasome inhibitor bortezomib in multiple myeloma therapy.

Bortezomib (BTZ), a proteasome inhibitor, has been widely used for the treatment of multiple myeloma (MM), including newly diagnosed as well as relapsed and refractory cases, and is considered to be a key drug in the induction therapy for MM. However, the precise mechanism underlying the action of this agent has yet to be fully elucidated. Predicting sensitivity to BTZ treatment by using adequate biomarkers would aid in the development of individual targeted therapies for MM. Herein, by reviewing preclinical studies using MM cell lines and other investigations that have analyzed primary MM samples from patients, we describe in detail the induction of MM cell death by proteasome inhibition and the factors that regulate the sensitivity of the proteasome inhibitor BTZ in MM cells.