title: The proteasome: mechanisms of biology and markers of activity and response to treatment in multiple myeloma.
abstract: Since the early 1990s, the synthesis and subsequent clinical application of small molecule inhibitors of the ubiquitin proteasome pathway (UPP) has revolutionized the treatment and prognosis of multiple myeloma. In this review, we summarize important aspects of the biology of the UPP with a focus on its structure and key upstream/downstream regulatory components. We then review current knowledge of plasma cell sensitivity to proteasome inhibition and highlight new proteasome inhibitors that have recently entered clinical development. Lastly, we address the putative role of circulating proteasomes as a novel biomarker in multiple myeloma and provide guidance for future clinical trials using proteasome inhibitors.
authors.affiliation: Multiple Myeloma Section, Metabolism Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA.
authors.forename: Elisabet E
authors.initials: EE
authors.lastname: Manasanch
authors.forename: Neha
authors.initials: N
authors.lastname: Korde
authors.forename: Adriana
authors.initials: A
authors.lastname: Zingone
authors.forename: Nishant
authors.initials: N
authors.lastname: Tageja
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez de Larrea
authors.forename: Manisha
authors.initials: M
authors.lastname: Bhutani
authors.forename: Peter
authors.initials: P
authors.lastname: Wu
authors.forename: Mark
authors.initials: M
authors.lastname: Roschewski
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D015415:Biomarkers; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex
keywords: Myeloma; cell cycle and apoptosis changes; prognostication