Iron and Micronutrient Deficiencies as Drivers of Carcinogenesis and Therapeutic Resistance in Cancer: An In-Depth Clinical and Physiological Three-Part Review - Part I—Iron Deficiency, Insufficiency, Excess, and Neoplasia

The 2019 Nobel Prize in Physiology or Medicine underscored a fundamental insight: cellular oxygen-sensing and hypoxia pathways orchestrate key biological responses, including the initiation and progression of cancer. Building on this framework, this review translates the core science of oxidative stress and hypoxia-driven molecular alterations into practical clinical strategies. Latent iron deficiency and iron overload are both common, frequently underdiagnosed, and potent mediators of redox activity capable of driving carcinogenesis.

This manuscript presents a mechanistic narrative review of how iron deficiency and iron overload generate reactive oxygen species (ROS), promote tumor initiation, progression, and resistance to therapy.

Emphasis is placed on equipping clinicians who manage patients with hereditary cancer predisposition, subclinical premalignant lesions, or early biomarkers of oncogenesis to recognize iron imbalance earlier and implement targeted surveillance and timely intervention before developing neoplastic lesions.