Protein degradation by proteasome is essential to the regulation of important cellular functions including cell cycle progression, proliferation, differentiation and apoptosis. Abnormal proteasomal degradation of key regulatory proteins perturbs the normal dynamics of these cellular processes culminating in uncontrolled cell cycle progression and decreased apoptosis leading to the characteristic @entity5 cell phenotype. Proteasome inhibitors are a novel group of therapeutic agents designed to oppose the increased proteasomal degradation observed in various @entity5 while restoring key cellular functions such as apoptosis, cell cycle progression, and the inhibition of angiogenesis. Several proteasome inhibitors have been evaluated in pre- and clinical studies for their potential usage in clinical oncology. @entity1749 (Velcade, @entity1749 ) is the first Food and Drug Administration-approved proteasome inhibitor for the treatment of @entity1582 and @entity1073 . @entity1749 's ability to preferentially induce @entity137 and cell death in @entity5 cells while rendering healthy cells unaffected makes it a powerful therapeutic agent and has extended its use in other types of @entity5 . The ability of @entity1749 and other proteasome inhibitors to synergize with conventional therapies in killing @entity5 in various in vitro and in vivo models makes this class of drugs a powerful tool in overcoming acquired and inherent resistance observed in many @entity5 . This is achieved through modulation of aberrant cellular survival signal transduction pathways and their downstream anti-apoptotic gene products. This review will discuss the anti-neoplastic effects of various proteasome inhibitors in a variety of @entity5 with a special emphasis on @entity1749 , its mechanism of action and role in @entity5 therapy. We further discuss the potential use of @entity1749 in the treatment of @entity320 .

Potential usage of proteasome inhibitor XXXX (Velcade, @entity1749 ) in the treatment of @entity320 : basic and clinical aspects.

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'cancers', 'cancer', 'malignancies'] @entity1582 :: ('MESH:D009101', 'Disease') :: ['multiple myeloma'] @entity1073 :: ('MESH:D020522', 'Disease') :: ['mantle cell lymphoma'] @entity1749 :: ('MESH:C400082', 'Chemical') :: ['bortezomib', 'PS-341', 'Bortezomib'] @entity320 :: ('MESH:D008545', 'Disease') :: ['metastatic melanoma']
@entity1749 :: (MESH:C400082,Chemical) :: ['bortezomib']
