Iron Metabolism and Cancer Risk

Iron is central to cellular respiration, DNA synthesis and oxygen transport. Its homeostasis is governed by coordinated processes of uptake, storage, utilisation and export, mediated by proteins such as transferrin, ferritin, ferroportin and hepcidin. Dysregulation of these pathways can lead to iron overload, driving carcinogenesis through the generation of reactive oxygen species via Fenton chemistry, DNA damage, aberrant signal transduction and enhanced proliferation. Conversely, iron deprivation may promote genomic instability, impair immune function and confer resistance to therapy. Tumour cells often reprogramme iron metabolism—increasing iron import and retention while evading iron‐dependent cell death pathways such as ferroptosis—to support rapid growth and survival. Understanding the dualistic role of iron in tumour initiation, progression and response to treatment has profound implications for global health, informing the development of biomarkers, dietary guidelines and novel therapeutic strategies, including iron chelation and ferroptosis induction.

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Iron Metabolism and Cancer Risk publication trend

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

Technical terms

Transferrin receptor (TFRC): A cell-surface protein mediating the uptake of transferrin-bound iron into cells.

Ferroptosis: A form of regulated cell death driven by iron-dependent lipid peroxidation and oxidative membrane damage.

Fenton reaction: A chemical reaction in which iron catalyses the conversion of hydrogen peroxide into highly reactive hydroxyl radicals.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can damage cellular structures and DNA.

Iron chelation: The therapeutic sequestration of free iron to prevent its participation in pro-oxidant reactions.

Tumour microenvironment: The complex milieu of non-malignant cells, extracellular matrix and signalling molecules surrounding cancer cells.

References

1. Transferrin Receptor‐Mediated Iron Uptake Promotes Colon Tumorigenesis. Advanced Science (2023).
2. Iron Supplementation Increases Tumor Burden and Alters Protein Expression in a Mouse Model of Human Intestinal Cancer. Nutrients (2024).
3. Insight into Iron, Oxidative Stress and Ferroptosis: Therapy Targets for Approaching Anticancer Strategies. Cancers (2024).
4. Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities. Protein & Cell (2014).