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Updated: Oct 18, 2025

Author Spotlight: Assessing the Impact of Novel Iron Chelators on Cancer Cell Metabolism
Published on: February 23, 2024
Iron-Sulfur Cluster Biogenesis as a Critical Target in Cancer
Michael S Petronek1,2, Douglas R Spitz1,2, Bryan G Allen1,2
1Department of Radiation Oncology, Division of Free Radical and Radiation Biology, The University of Iowa Hospitals and Clinics, Iowa City, IA 52242-1181, USA.
Abstract:
Cancer cells preferentially accumulate iron (Fe) relative to non-malignant cells; however, the underlying rationale remains elusive. Iron-sulfur (Fe-S) clusters are critical cofactors that aid in a wide variety of cellular functions (e.g., DNA metabolism and electron transport). In this article, we theorize that a differential need for Fe-S biogenesis in tumor versus non-malignant cells underlies the Fe-dependent cell growth demand of cancer cells to promote cell division and survival by promoting genomic stability via Fe-S containing DNA metabolic enzymes. In this review, we outline the complex Fe-S biogenesis process and its potential upregulation in cancer. We also discuss three therapeutic strategies to target Fe-S biogenesis: (i) redox manipulation, (ii) Fe chelation, and (iii) Fe mimicry.
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