Abstract
The proteasome has been regarded as a major target for antitumor therapy in selected tumor types (i.e., multiple myeloma). Available evidence suggests that targeting the proteasome with selective compounds can represent an excellent approach for modulating the response to antitumor agents including both conventional cytotoxic agents and target-specific agents. In fact, promising drug interaction data showing synergistic effects have been reported in cellular studies, both in multiple myeloma and in solid tumors. The mechanistic bases of improved efficacy of drug combinations including bortezomib or other proteasome inhibitors and conventional cytotoxic agents have been in part unravelled and involve the capability of proteasome inhibitors to interfere with the stability of the targets of cytotoxic agents (e.g., topoisomerase inhibitors) as well as with cellular protective pathways (e.g., DNA repair and NF-kB-regulated gene expression). Moreover, the synergistic interaction of proteasome inhibitors and target-specific agents implicates a variety of mechanisms linked to the specific target (e.g., histone deacetylase) modulated by the tailored drug used in combination with the proteasome inhibitor. Several clinical studies are ongoing in an attempt to define drug combination approaches that enhance the efficacy of antitumor treatments. Considering the fast moving field of preclinical research regarding proteasome inhibition, a major contribution to the understanding of the bases of tumor response to treatment with proteasome inhibitors is expected.
Keywords: Proteasome, combination treatment, cytotoxic agents, target-specific agents.
Current Pharmaceutical Design
Title:Drug Combinations with Proteasome Inhibitors in Antitumor Therapy
Volume: 19 Issue: 22
Author(s): Laura Gatti, Valentina Zuco, Nadia Zaffaroni and Paola Perego
Affiliation:
Keywords: Proteasome, combination treatment, cytotoxic agents, target-specific agents.
Abstract: The proteasome has been regarded as a major target for antitumor therapy in selected tumor types (i.e., multiple myeloma). Available evidence suggests that targeting the proteasome with selective compounds can represent an excellent approach for modulating the response to antitumor agents including both conventional cytotoxic agents and target-specific agents. In fact, promising drug interaction data showing synergistic effects have been reported in cellular studies, both in multiple myeloma and in solid tumors. The mechanistic bases of improved efficacy of drug combinations including bortezomib or other proteasome inhibitors and conventional cytotoxic agents have been in part unravelled and involve the capability of proteasome inhibitors to interfere with the stability of the targets of cytotoxic agents (e.g., topoisomerase inhibitors) as well as with cellular protective pathways (e.g., DNA repair and NF-kB-regulated gene expression). Moreover, the synergistic interaction of proteasome inhibitors and target-specific agents implicates a variety of mechanisms linked to the specific target (e.g., histone deacetylase) modulated by the tailored drug used in combination with the proteasome inhibitor. Several clinical studies are ongoing in an attempt to define drug combination approaches that enhance the efficacy of antitumor treatments. Considering the fast moving field of preclinical research regarding proteasome inhibition, a major contribution to the understanding of the bases of tumor response to treatment with proteasome inhibitors is expected.
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Cite this article as:
Gatti Laura, Zuco Valentina, Zaffaroni Nadia and Perego Paola, Drug Combinations with Proteasome Inhibitors in Antitumor Therapy, Current Pharmaceutical Design 2013; 19 (22) . https://dx.doi.org/10.2174/1381612811319220015
DOI https://dx.doi.org/10.2174/1381612811319220015 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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