Bortezomib action in multiple myeloma: microRNA-mediated synergy (and miR-27a/CDK5 driven sensitivity)?

Bortezomib (PS-341; Velcade) is a reversible inhibitor of the 26S proteasome that produces significant clinical responses in both newly diagnosed and advanced multiple myeloma (MM). However, only 40% of patients respond to bortezomib as a single-agent therapy, and most of those will become resistant. Consequently, understanding the mechanism of action of bortezomib is of great interest. Although the inhibitory activity of bortezomib is clearly defined, the downstream mechanisms of cytotoxity remain poorly understood and at times controversial. 1 There is now emerging evidence that microRNAs (miRNAs) are important factors in anticancer drug activity and resistance. 2 We therefore decided to investigate the potential involvement of miRNAs in the action of bortezomib on MM cells.