Iron Dysregulation in Human Cancer: Altered Metabolism, Biomarkers for Diagnosis, Prognosis, Monitoring and Rationale for Therapy

SIMPLE SUMMARY: Iron is the more abundant metal ion in humans. It is essential for life as it has a role in various cellular processes involved, for instance, in cell metabolism and DNA synthesis. These functions are crucial for cell proliferation, and it is therefore not surprising that iron is accumulated in tumors. In this review, we describe normal and altered iron homeostasis mechanisms. We also provide a vision of iron-related proteins with altered expression in cancers and discuss their potential as diagnostic and/or prognostic biomarkers. Finally, we give an overview of therapeutic strategies acting on iron metabolism to fight against cancers. ABSTRACT: Iron (Fe) is a trace element that plays essential roles in various biological processes such as DNA synthesis and repair, as well as cellular energy production and oxygen transport, and it is currently widely recognized that iron homeostasis is dysregulated in many cancers. Indeed, several iron homeostasis proteins may be responsible for malignant tumor initiation, proliferation, and for the metastatic spread of tumors. A large number of studies demonstrated the potential clinical value of utilizing these deregulated proteins as prognostic and/or predictive biomarkers of malignancy and/or response to anticancer treatments. Additionally, the iron present in cancer cells and the importance of iron in ferroptosis cell death signaling pathways prompted the development of therapeutic strategies against advanced stage or resistant cancers. In this review, we select relevant and promising studies in the field of iron metabolism in cancer research and clinical oncology. Besides this, we discuss some co-existing discrepant findings. We also present and discuss the latest lines of research related to targeting iron, or its regulatory pathways, as potential promising anticancer strategies for human therapy. Iron chelators, such as deferoxamine or iron-oxide-based nanoparticles, which are already tested in clinical trials, alone or in combination with chemotherapy, are also reported.