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Published in: Cancer and Metastasis Reviews 4/2017

01-12-2017

Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing

Authors: Claire L. Soave, Tracey Guerin, Jinbao Liu, Q. Ping Dou

Published in: Cancer and Metastasis Reviews | Issue 4/2017

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Abstract

In the past 15 years, the proteasome has been validated as an anti-cancer drug target and 20S proteasome inhibitors (such as bortezomib and carfilzomib) have been approved by the FDA for the treatment of multiple myeloma and some other liquid tumors. However, there are shortcomings of clinical proteasome inhibitors, including severe toxicity, drug resistance, and no effect in solid tumors. At the same time, extensive research has been conducted in the areas of natural compounds and old drug repositioning towards the goal of discovering effective, economical, low toxicity proteasome-inhibitory anti-cancer drugs. A variety of dietary polyphenols, medicinal molecules, metallic complexes, and metal-binding compounds have been found to be able to selectively inhibit tumor cellular proteasomes and induce apoptotic cell death in vitro and in vivo, supporting the clinical success of specific 20S proteasome inhibitors bortezomib and carfilzomib. Therefore, the discovery of natural proteasome inhibitors and researching old drugs with proteasome-inhibitory properties may provide an alternative strategy for improving the current status of cancer treatment and even prevention.
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Metadata
Title
Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing
Authors
Claire L. Soave
Tracey Guerin
Jinbao Liu
Q. Ping Dou
Publication date
01-12-2017
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 4/2017
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-017-9705-x

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