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Expert Opin Ther Targets. 2013 Sep;17(9):1091-108. doi: 10.1517/14728222.2013.815728. Epub 2013 Jul 4.

Targeting the ubiquitin-proteasome system for cancer therapy.

Author information

1
Wayne State University, Barbara Ann Karmanos Cancer Institute, School of Medicine, Department of Pharmacology, Detroit, MI 48201, USA.

Abstract

INTRODUCTION:

The ubiquitin-proteasome system (UPS) degrades 80 - 90% of intracellular proteins. Cancer cells take advantage of the UPS for their increased growth and decreased apoptotic cell death. Thus, the components that make up the UPS represent a diverse group of potential anti-cancer targets. The success of the first-in-class proteasome inhibitor bortezomib not only proved that the proteasome is a feasible and valuable anti-cancer target, but also inspired researchers to extensively explore other potential targets of this pathway.

AREAS COVERED:

This review provides a broad overview of the UPS and its role in supporting cancer development and progression, especially in aspects of p53 inactivation, p27 turnover and NF-κB activation. Also, efforts toward the development of small molecule inhibitors (SMIs) targeting different steps in this pathway for cancer treatment are reviewed and discussed.

EXPERT OPINION:

Whereas some of the targets in the UPS, such as the 20S proteasome, Nedd8 activating enzyme and HDM2, have been well-established and validated, there remains a large pool of candidates waiting to be investigated. Development of SMIs targeting the UPS has been largely facilitated by state-of-the-art technologies such as high-throughput screening and computer-assisted drug design, both of which require a better understanding of the targets of interest.

PMID:
23822887
PMCID:
PMC3773690
DOI:
10.1517/14728222.2013.815728
[Indexed for MEDLINE]
Free PMC Article

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