title: Proteasome inhibition in multiple myeloma.
abstract: The ubiquitin-proteasome pathway is the major cellular degradative system for various proteins critical for proliferation, survival and homing of myeloma cells. Bortezomib is the first specific and reversible proteasome inhibitor for clinical application in humans. Phase I studies have defined the maximum tolerated dose and suggested activity against multiple myeloma. From single agent phase II studies, a rate of at least partial responses ranging from 27% for relapsed and refractory to 38% for second-line patients was derived. In comparison with pulsed dexamethasone, bortezomib enabled a higher response rate, a longer time to myeloma progression and a longer survival for patients after one to three prior lines of therapy. Preclinical and clinical phase I studies as well as initial phase II studies combining bortezomib with conventional chemotherapy or thalidomide support the assumption that bortezomib sensitizes myeloma cells to these drugs resulting in additive or synergistic activity.
authors.affiliation: Department of Medicine/Haematology and Oncology, University of Münster, Albert-Schweitzer-Str. 33, 48149 Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kropff
authors.forename: Guido
authors.initials: G
authors.lastname: Bisping
authors.forename: Doris
authors.initials: D
authors.lastname: Wenning
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Joachim
authors.initials: J
authors.lastname: Kienast
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib; D003907:Dexamethasone