Copper complexes in cancer therapy

Denoyer, Delphine, Clatworthy, Sharnel AS and Cater, Michael A 2018, Copper complexes in cancer therapy. In Sigel, Astrid, Sigel, Helmut, Freisinger, Eva and Sigel, Roland KO (ed), Metallo-drugs: development and action of anticancer agents, De Gruyter, Berlin, Germany, pp.469-506, doi: 10.1515/9783110470734-022.

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Title Copper complexes in cancer therapy
Author(s) Denoyer, DelphineORCID iD for Denoyer, Delphine orcid.org/0000-0001-8932-5116
Clatworthy, Sharnel AS
Cater, Michael A
Title of book Metallo-drugs: development and action of anticancer agents
Editor(s) Sigel, Astrid
Sigel, Helmut
Freisinger, Eva
Sigel, Roland KO
Publication date 2018
Series Metal ions in life sciences
Chapter number 16
Total chapters 17
Start page 469
End page 506
Total pages 38
Publisher De Gruyter
Place of Publication Berlin, Germany
Keyword(s) cancer
chelator
clioquinol
disulfiram
elesclomol
ionophore
tetrathiomolybdate
thiosemicarbazones
Summary Copper homeostasis is tightly regulated in both prokaryotic and eukaryotic cells to ensure sufficient amounts for cuproprotein biosynthesis, while limiting oxidative stress production and toxicity. Over the last century, copper complexes have been developed as antimicrobials and for treating diseases involving copper dyshomeostasis (e.g., Wilson's disease). There now exists a repertoire of copper complexes that can regulate bodily copper through a myriad of mechanisms. Furthermore, many copper complexes are now being appraised for a variety of therapeutic indications (e.g., Alzheimer's disease and amyotrophic lateral sclerosis) that require a range of copper-related pharmacological affects. Cancer therapy is also drawing considerable attention since copper has been recognized as a limiting factor for multiple aspects of cancer progression including growth, angiogenesis, and metastasis. Consequently, 'old copper complexes' (e.g., tetrathiomolybdate and clioquinol) have been repurposed for cancer therapy and have demonstrated anticancer activity in vitro and in preclinical models. Likewise, new tailor-made copper complexes have been designed based on structural and biological features ideal for their anticancer activity. Human clinical trials continue to evaluate the therapeutic efficacy of copper complexes as anticancer agents and considerable progress has been made in understanding their pharmacological requirements. In this chapter, we present a historical perspective on the main copper complexes that are currently being repurposed for cancer therapy and detail several of the more recently developed compounds that have emerged as promising anticancer agents. We further provide an overview of the known mechanisms of action, including molecular targets and we discuss associated clinical trials.
ISBN 978-3-11-046984-4
ISSN 1559-0836
1868-0402
Language eng
DOI 10.1515/9783110470734-022
HERDC Research category B1 Book chapter
ERA Research output type B Book chapter
Copyright notice ©2018, Walter de Gruyter GmbH, Berlin/Boston
Persistent URL http://hdl.handle.net/10536/DRO/DU:30107609

Document type: Book Chapter
Collection: School of Life and Environmental Sciences
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