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Review
. 2023 Jun:74:102315.
doi: 10.1016/j.cbpa.2023.102315. Epub 2023 May 13.

Targeting iron to contrast cancer progression

Elisa Tomat  1
Affiliations
Review

Targeting iron to contrast cancer progression

Elisa Tomat. Curr Opin Chem Biol. 2023 Jun.

Abstract

An altered metabolism of iron fuels cancer growth, invasion, metastasis, and recurrence. Ongoing research in cancer biology is delineating a complex iron-trafficking program involving both malignant cells and their support network of cancer stem cells, immune cells, and other stromal components in the tumor microenvironment. Iron-binding strategies in anticancer drug discovery are being pursued in clinical trials and in multiple programs at various levels of development. Polypharmacological mechanisms of action, combined with emerging iron-associated biomarkers and companion diagnostics, are poised to offer new therapeutic options. By targeting a fundamental player in cancer progression, iron-binding drug candidates (either alone or in combination therapy) have the potential to impact a broad range of cancer types and to address the major clinical problems of recurrence and resistance to therapy.

Keywords: Cancer; Chelator; Iron; Macrophage; Prochelator; Stemness; Tumor microenvironment.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Simplified schematic showing the key components of the cellular iron import-export machinery. In cancer cells, a larger labile iron pool is maintained through the overexpression of the transferrin receptor TfR1, transporter DMT1, and STEAP metalloreductases, as well as through the downregulation of iron exporter FPN mediated by hormone hepcidin.
Figure 2.
Figure 2.
Examples of iron chelators studied for anticancer applications with known iron-binding units shown in blue.
Figure 3.
Figure 3.
Examples of iron prochelation strategies showing the activation reactions that release antiproliferative chelators (with confirmed binding units in blue).
See this image and copyright information in PMC

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