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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...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886336/ https://www.ncbi.nlm.nih.gov/pubmed/20616904 |
Sumario: | 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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