Copper: An Intracellular Achilles' Heel Allowing the Targeting of Epigenetics, Kinase Pathways, and Cell Metabolism in Cancer Therapeutics.

Autor: Michniewicz F; Children's Cancer Institute, Lowy Cancer Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia., Saletta F; Children's Cancer Institute, Lowy Cancer Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia., Rouaen JRC; Children's Cancer Institute, Lowy Cancer Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia., Hewavisenti RV; Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia., Mercatelli D; Department of Pharmacy and Biotechnology, University of Bologna, 40126, Bologna, Italy., Cirillo G; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, Italy., Giorgi FM; Department of Pharmacy and Biotechnology, University of Bologna, 40126, Bologna, Italy., Trahair T; Children's Cancer Institute, Lowy Cancer Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia., Ziegler D; Children's Cancer Institute, Lowy Cancer Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia., Vittorio O; Children's Cancer Institute, Lowy Cancer Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2021 Aug 05; Vol. 16 (15), pp. 2315-2329. Date of Electronic Publication: 2021 Jun 01.
DOI: 10.1002/cmdc.202100172
Abstrakt: 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.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: