Iron chelators in breast cancer therapy - mechanisms and clinical applications - a narrative review

Sep 23, 2026

Iron is an essential element for cell growth and metabolism, yet its dysregulation is central to cancer pathogenesis, including breast cancer. Cancer cells often depend on elevated iron to sustain rapid proliferation, making iron chelation a promising therapeutic strategy. Iron chelators bind free intracellular iron, disrupt critical biological processes, trigger oxidative stress, impair DNA repair, and disturb iron homeostasis, leading to cancer cell death. Clinical and preclinical studies indicate that iron depletion can sensitize tumors to chemotherapy and radiotherapy, while newer tumor-selective agents aim to reduce off-target effects. Additional optimization is still required for routine clinical use.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Abstract

Introduction

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Iron chelation and its role in cancer biology

Review Iron chelators in breast cancer therapy: mechanisms and clinical applications – a narrative review Emmanuel Ifeanyi Obeagu, PhDa ,*, Anthonia Onyinye Ngwoke, MBBS, MScb , Garikai Malunga, MSca Abstract Iron is an essential element for cell growth and metabolism, but its dysregulation is a key feature in the pathogenesis of various cancers, including breast cancer. Cancer cells require elevated iron levels to support their rapid growth, and as such, iron chelation has emerged as a promising therapeutic strategy. Iron chelators work by binding free iron in cancer cells, preventing its use in critical biological processes and thereby disrupting tumor cell proliferation. This review discusses the mechanisms of action of iron chelators in breast cancer therapy, highlighting how they induce oxidative stress, impair DNA repair, and alter cellular iron homeostasis, ultimately leading to cancer cell death. Iron chelation therapy has been explored in several clinical and preclinical studies for its potential to enhance the effectiveness of conventional breast cancer treatments, including chemotherapy and radiotherapy. By depleting intracellular iron, iron chelators can sensitize cancer cells to these treatments, increasing the cytotoxic effects and improving patient outcomes. Additionally, novel iron chelators with higher specificity for tumor cells are being developed, which aim to minimize off-target effects and enhance therapeutic efficacy. While iron chelation therapy has shown promise in early-phase trials, further research is needed to optimize these agents for clinical use in breast cancer treatment. Keywords: breast cancer therapy, clinical applications, iron chelators, mechanisms, targeted therapy Introduction Iron is a crucial element for various cellular processes, including DNA synthesis, mitochondrial function, and cellular respiration. It plays a central role in maintaining the cell’s metabolic activities and supporting growth and division. In normal cells, iron is tightly regulated through complex mechanisms that ensure an adequate supply while preventing its excess, which can result in oxidative stress and cellular damage. However, cancer cells, including those in breast cancer, often exhibit altered iron metabolism, with increased iron uptake and reduced storage or efflux, facilitating their rapid growth and survival in the tumor microenvironment. Dysregulated iron homeostasis in tumors has become a hallmark of cancer biology, and its potential for therapeutic targeting is an area of significant interest[1,2] . Breast cancer is one of the most prevalent cancers worldwide, accounting for a substantial number of cancer diagnoses and aDepartment of Biomedical and Laboratory Science, Africa University, Zimbabwe and bDepartment of Human Physiology, Faculty of Basic Medical Sciences, Enugu State University of Science and Technology, Enugu, Nigeria Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department ofBiomedical and Laboratory Science, Africa University, Mutare, Zimbabwe. Tel.: +2348037369912. [E-mail: emmanuelobeagu@yahoo.com](E-mail: emmanuelobeagu@yahoo.com) (E. I. Obeagu). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Annals of Medicine & Surgery (2025) 87:3556–3565 Received 15 March 2025; Accepted 4 April 2025 Published online 25 April 2025 [http://dx.doi.org/10.1097/MS9.0000000000003296](http://dx.doi.org/10.1097/MS9.0000000000003296) HIGHLIGHTS ● Tumor suppression: Iron chelators deplete intracellular iron, hindering breast cancer cell growth and survival. ● Reactive oxygen species modulation: Chelators reduce reactive oxygen spec

FAQs

How do iron chelators exert antitumor effects in breast cancer?

They bind free iron in cancer cells, disrupting iron-dependent biological processes. This can promote oxidative stress, impair DNA repair, and disturb cellular iron homeostasis, ultimately leading to cancer cell death.

Why is iron metabolism important for breast cancer progression?

Breast cancer cells often show altered iron metabolism with increased uptake and reduced storage or efflux. This supports rapid growth in the tumor microenvironment and contributes to oxidative stress through iron-dependent reactions.

What is the clinical rationale for combining iron chelation with chemotherapy or radiotherapy?

Depleting intracellular iron can sensitize cancer cells to conventional treatments. This enhances cytotoxic effects and may improve patient outcomes, as suggested by preclinical and early clinical studies.

Sep 23, 2026

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