Cancer metabolism is a well-known target of cancer therapeutics. Classically, cancer metabolism has been studied in terms of the dependence of cancer cells on crucial metabolites, such as glucose and glutamine. But, the accumulating data show that iron metabolism in tumor microenvironment is also an important factor in preserving the survival of cancer cells. Cancer cells have a distinct phenotype of iron metabolism, which secures the much-needed iron for these metabolically active cells. In order to use this iron efficiently, cancer cells need to increase their iron supply and decrease iron loss. As recent research suggests, this is not only done by modifying the expression of iron-related proteins in cancer cells, but also by interaction of cancer cells with other cells from the tumor milieu. Tumor microenvironment is a dynamic environment characterized with intricate relationship between cancer cells, tumor-associated macrophages, fibroblasts, and other cells. Some of the mechanistic aspects of this relationship have been elucidated, while others are yet to be identified. In any case, identifying the details of the iron phenotype of the cells in tumor microenvironment presents with a new therapeutic opportunity to treat this deadly disease.
Keywords: Cancer stem cells; Cancer-associated fibroblasts; Divalent metal transporter 1; Ferritinophagy; Ferroportin; Ferroptosis; Hepcidin; Interleukin 6; Iron; Iron chelation; Nanomedicine; Transferrin receptor 1; Tumor microenvironment; Tumor-associated macrophages; Vacuolar ATPase.