Targeting proteasomes as therapy in multiple myeloma.

The Ubiquitin-proteasome pathway (UPP) regulates normal intracellular protein degradation processes essential for cell cycle progression, inflammation, transcription, DNA replication, and apoptosis. Blockade of UPP using proteasome inhibitor Bortezomib (Velcade) is an effective therapy for relapsed/refractory multiple myeloma (MM). Both oligonucleotide microarrays and proteomic studies are delineating the molecular mechanisms mediating Bortezomib-induced cytotoxicity, defining targets of sensitivity vs resistance, allowing for the development of next generation therapies, and providing the rationale for combination therapies.