title: The ubiquitin-proteasome system (UPS) and the mechanism of action of bortezomib.
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, bortezomib's mechanism of action remains elusive despite enormous progress in our knowledge of the cell biology of the ubiquitin-proteasome system (UPS) and bortezomib-induced signaling events in cancer cells. This review maps a rapidly growing and open body of research in both areas.
authors.affiliation: Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 11, 78371 Olomouc, Czech Republic. cvekb@seznam.cz
authors.forename: Boris
authors.initials: B
authors.lastname: Cvek
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex