Journal
CHEMMEDCHEM
Volume 16, Issue 15, Pages 2315-2329Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.202100172
Keywords
Copper; RTK; Epigenetics; Metabolism; Cancer
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Funding
- Australian Government Research Training Program (RTP) Scholarship
- Cure Cancer Australia, Cancer Institute of NSW Translational Grant
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Copper plays a crucial role in cancer progression by influencing cell processes, and overcoming drug resistance and relapse may require developing broader molecular targeting strategies. Overcoming these limitations may involve using copper chelating agents to simultaneously target multiple cancer treatment mechanisms.
Copper is an essential transition metal frequently increased in cancer known to strongly influence essential cellular processes. Targeted therapy protocols utilizing both novel and repurposed drug agents initially demonstrate strong efficacy, before failing in advanced cancers as drug resistance develops and relapse occurs. Overcoming this limitation involves the development of strategies and protocols aimed at a wider targeting of the underlying molecular changes. Receptor Tyrosine Kinase signaling pathways, epigenetic mechanisms and cell metabolism are among the most common therapeutic targets, with molecular investigations increasingly demonstrating the strong influence each mechanism exerts on the others. Interestingly, all these mechanisms can be influenced by intracellular copper. We propose that copper chelating agents, already in clinical trial for multiple cancers, may simultaneously target these mechanisms across a wide variety of cancers, serving as an excellent candidate for targeted combination therapy. This review summarizes the known links between these mechanisms, copper, and copper chelation therapy.
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