The Ubiquitin-Proteasome System (UPS) and the Mechanism of Action of Bortezomib

Boris      Cvek; Zdenek      Dvorak

doi:10.2174/138161211796197124

Abstract

Proteasome inhibition is a modern and surprisingly successful approach how to cancer treatment. Bortezomib (Velcade®) is a first-in-class proteasome inhibitor and has been approved for first-line treatment of multiple myeloma and second-line treatment of mantle cell lymphoma. There have been almost 200 clinical trials with bortezomib, both as a single agent and in combination with other drugs, for various cancers, as listed in the US National Cancer Institute database. However, bortezomibs mechanism of action remains elusive despite enormous progress in our knowledge of the cell biology of the ubiquitin-proteasome system (UPS) and bortezomibinduced signaling events in cancer cells. This review maps a rapidly growing and open body of research in both areas.

Keywords: Ubiquitin-proteasome system, bortezomib, mechanism of action, ubiquitin-proteasome, myeloma, lymphoma, aldehyde, calpain, murine, myelogenous, leukemia, tumorigenesis, tyrosine, deacetylases, polymerase, angiogenesis, emesis