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Bortezomib in Kidney Transplant: Current Use and Perspectives

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Date
2017
Author
Requiao-Moura, Lucio R.
de Sandes-Freitas, Taina V.
Marcelo-Gomes, Gessika [UNIFESP]
Rangel, Erika B.
Type
Artigo
ISSN
1389-2002
Is part of
Current Drug Metabolism
DOI
10.2174/1389200218666171121100716
Metadata
Show full item record
Abstract
Background: Despite major advances in transplant medicine, antibody-mediated rejection (AMR) continues to have severe clinical implications and adversely affect graft survival. Therefore, the search for alternative drugs to treat AMR is widely pursued. The first-in-class proteasome inhibitor bortezomib (BZ) is a selective inhibitor of the 26S proteasome, which was initially approved for the treatment of malignant plasma cell disorders. Methods: This review encompasses how our understanding of inhibiting proteasome pathway created the basis of BZ research and important milestones accomplished in AMR treatment in the transplant setting. It further discusses at length the results of clinical studies, the tolerability profile, drug-drug interactions and the perspectives of BZ use in desensitization protocols. Results: Proteasome inhibition can downregulate NF-kappa B activity
 
decrease cell proliferation/differentiation
 
induce apoptosis via cell cycle arrest, endoplasmic reticulum stress and caspase induction due the accumulation of unfolded or misfolded proteins
 
and downregulate antigen presentation, cell-cell interaction, and cell migration. Proteasome inhibition is more evident in cells with high rate of protein synthesis and secretion, like plasma cells. These cells play a critical role in the production of antibodies during AMR. Conclusions: There is accumulating evidence that the proteasome inhibitor BZ may substantially affect the function and integrity of alloantibody-secreting plasma cells in AMR after organ solid transplant, as well as the activation, proliferation and differentiation of T-and B-lymphocytes. Recent clinical studies have provided evidence that BZ has the capability to downregulate circulating antibodies and treat AMR episodes. Additional randomized-controlled studies are required to assess the impact of BZ during short and long follow-ups.
 
Citation
Current Drug Metabolism. Sharjah, v. 18, n. 12, p. 1136-1146, 2017.
Keywords
Bortezomib
proteasome inhibition
antibody-mediated rejection
kidney transplant
donor specific antibodies
adverse events
URI
https://repositorio.unifesp.br/handle/11600/55335
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  • EPM - Artigos [16302]

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