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The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib

The ubiquitin–proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341) is a potent and specific reversible proteasome...

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Detalles Bibliográficos
Autores principales: Milano, A, Perri, F, Caponigro, F
Formato: Texto
Lenguaje:English
Publicado: Dove Medical Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886336/
https://www.ncbi.nlm.nih.gov/pubmed/20616904
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author Milano, A
Perri, F
Caponigro, F
author_facet Milano, A
Perri, F
Caponigro, F
author_sort Milano, A
collection PubMed
description The ubiquitin–proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341) is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies. In preclinical studies, bortezomib induced apoptosis of malignant cells through the inhibition of NF-|B and stabilization of pro-apoptotic proteins. Bortezomib also promotes chemo- and radiosensitization of malignant cells in vitro and inhibits tumor growth in murine xenograft models. The proteasome has been established as a relevant target in hematologic malignancies and bortezomib has been approved for the treatment of multiple myeloma. This review summarizes recent data from clinical trials in solid tumors.
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spelling pubmed-28863362010-07-08 The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib Milano, A Perri, F Caponigro, F Onco Targets Ther Review The ubiquitin–proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341) is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies. In preclinical studies, bortezomib induced apoptosis of malignant cells through the inhibition of NF-|B and stabilization of pro-apoptotic proteins. Bortezomib also promotes chemo- and radiosensitization of malignant cells in vitro and inhibits tumor growth in murine xenograft models. The proteasome has been established as a relevant target in hematologic malignancies and bortezomib has been approved for the treatment of multiple myeloma. This review summarizes recent data from clinical trials in solid tumors. Dove Medical Press 2009-02-18 /pmc/articles/PMC2886336/ /pubmed/20616904 Text en © 2009 Milano et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
Milano, A
Perri, F
Caponigro, F
The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib
title The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib
title_full The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib
title_fullStr The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib
title_full_unstemmed The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib
title_short The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib
title_sort ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886336/
https://www.ncbi.nlm.nih.gov/pubmed/20616904
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