Iron Chelation Strategies in Cancer Therapy

Iron is fundamental for tumour cell proliferation, engaging in DNA synthesis, respiration and redox processes. Cancer cells commonly upregulate iron uptake pathways and adapt their microenvironment to sustain a high labile iron pool, promoting growth and evading oxidative stress. Iron chelation has emerged as a dual‐purpose approach: depriving malignant cells of essential iron cofactors and inducing cytotoxicity through redox imbalance. Small‐molecule chelators target ribonucleotide reductase, disrupt mitochondrial respiration and trigger regulated cell death pathways such as ferroptosis. These agents can affect both actively dividing and quiescent tumour subsets, offering a strategy to overcome heterogeneity and drug resistance. Combinatorial regimens integrating iron chelators with conventional cytotoxics or targeted therapies have shown enhanced antitumour effects, suggesting translational potential for diverse malignancies.

Research from Nature Portfolio

Studies have revealed that certain iron‐binding compounds exert anticancer activity by simultaneously inhibiting ribonucleotide reductase and impairing mitochondrial energy production, creating metabolic stress intolerable to tumour cells with limited vascular support. This dual action effectively targets both proliferative and quiescent populations within solid tumours. Structure–activity relationship analyses confirmed that these agents chelate ferrous and ferric iron, and rescue experiments with exogenous iron reversed their bioactivity, underscoring the mechanistic basis for antineoplastic effects. This work highlights chelators as versatile molecules capable of exploiting iron dependency and metabolic vulnerabilities in heterogeneous cancer microenvironments.

Iron Chelation Strategies in Cancer Therapy publication trend

The graph below shows the total number of articles in iron chelation strategies in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Iron chelator: A molecule that binds free iron ions, preventing their participation in cellular redox reactions and enzyme cofactors.

Labile iron pool (LIP): The readily exchangeable intracellular iron fraction available for metabolic processes.

Ferroptosis: A regulated form of cell death driven by iron‐dependent lipid peroxidation.

Ribonucleotide reductase: An enzyme essential for deoxyribonucleotide synthesis, requiring iron as a cofactor.

Transferrin receptor: A cell-surface protein that mediates iron uptake via transferrin binding and endocytosis.

Lysosomotropic: Characteristic of compounds that accumulate preferentially within lysosomes.

References

1. Ironomycin induces mantle cell lymphoma cell death by targeting iron metabolism addiction. Theranostics (2025).
2. Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia. Leukemia (2024).
3. Iron chelators target both proliferating and quiescent cancer cells. Scientific Reports (2016).
4. Iron as a Central Player and Promising Target in Cancer Progression. International Journal of Molecular Sciences (2019).