Abstract
Demanded as an essential trace element that supports cell growth and basic functions, iron can be harmful and cancerogenic though. By exchanging between its different oxidized forms, iron overload induces free radical formation, lipid peroxidation, DNA, and protein damages, leading to carcinogenesis or ferroptosis. Iron also plays profound roles in modulating tumor microenvironment and metastasis, maintaining genomic stability and controlling epigenetics. in order to meet the high requirement of iron, neoplastic cells have remodeled iron metabolism pathways, including acquisition, storage, and efflux, which makes manipulating iron homeostasis a considerable approach for cancer therapy. Several iron chelators and iron oxide nanoparticles (IONPs) has recently been developed for cancer intervention and presented considerable effects. This review summarizes some latest findings about iron metabolism function and regulation mechanism in cancer and the application of iron chelators and IONPs in cancer diagnosis and therapy.
Highlights
The past decade has been described as the “golden age” of iron metabolism, due to the discovery of new iron-related proteins and regulatory mechanisms [1]
The expressions of numerous iron metabolism-related proteins are aberrantly regulated in malignant tumors, and a variety of signaling pathways and physiological processes are altered by iron in cancer, manifesting the essential roles of iron in cancer development
Aberrant iron homeostasis is to some extent a hallmark of cancer
Summary
The past decade has been described as the “golden age” of iron metabolism, due to the discovery of new iron-related proteins and regulatory mechanisms [1]. Multiple iron metabolism-associated proteins have been proved to participate in malignant tumor initiation, proliferation, and metastasis. Tumor cells differ in the expressions or activities of many iron-related proteins. These alterations generally contribute to a relatively high level of intracellular iron availability and facilitate the functions of iron-dependent proteins, which are involved in numerous physiological processes including DNA synthesis and repair, cell cycle regulation, angiogenesis, metastasis, tumor microenvironment, and epigenetic remodeling [2,3]. Iron homeostasis modulations including iron depletion and iron metabolism-targeted treatments have exhibit potent and broad anti-tumor effect, which makes it a potential and largely undeveloped therapeutic target for cancer pharmacological therapy. We summarize some novel iron modulators in development and iron chelators in combined therapy, which could provide new therapeutic options for cancer intervention
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