The role of iron metabolism in cancer therapy focusing on tumor‐associated macrophages

Iron is an essential micronutrient in mammalian cells for basic processes such as DNA synthesis, cell cycle progression, and mitochondrial activity. Macrophages play a vital role in iron metabolism, which is tightly linked to their phagocytosis of senescent and death erythrocytes. It is now recognized that the polarization process of macrophages determines the expression profile of genes associated with iron metabolism. Although iron metabolism is strictly controlled by physiology, cancer has recently been connected with disordered iron metabolism. Moreover, in the environment of cancer, tumor‐associated macrophages (TAMs) exhibit an iron release phenotype, which stimulates tumor cell survival and growth. Usually, the abundance of TAMs in the tumor is implicated in poor disease prognosis. Therefore, important attention has been drawn toward the development of tumor immunotherapies targeting these TAMs focussing on iron metabolism and reprogramming polarized phenotypes. Although further systematic research is still required, these efforts are almost certainly valuable in the search for new and effective cancer treatments. The iron metabolic pathways of cancer cells and macrophages are summarized. A vicious alliance of iron and macrophages in the tumor microenvironment is diagrammatized. Targeting tumor‐associated macrophages based on iron metabolism constitutes a promising therapeutic for cancer therapy.