Cancer
The body's need for iron is regulated by a variety of factors and mechanisms, and dysregulation of iron homeostasis due to genetic and lifestyle factors may lead to an increased risk of developing cancer. Cancer cells are characterized by rapid proliferation and therefore require more iron and result in dysregulated levels of key proteins involved in iron metabolism.
Iron Metabolism Dysregulation in Cancer
The rapid growth characteristics of cancer cells are maintained due to altered gene expression that favors the import and retention of iron. These transformations may be regulated at different time points and affect the biosynthetic and proliferative state of the cells. At the same time, cancer cells exploit the cellular antioxidant system to avoid cellular damage caused by iron toxicity.
- Dysregulation of Systemic Iron Metabolism in Cancer
Systemic dysregulation of iron homeostasis is commonly seen in patients with cancer and manifests as decreased red blood cell count or anemia. Anemia due to cancer is usually considered to be inflammatory anemia. Mechanistically, cancer-induced anemia is mediated by the secretion of inflammatory factors, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6). TNF α contributes to the inhibition of erythropoiesis, while IL-6 drives iron limitation through upregulation of iron-regulated hormones. - Dysregulation of Cellular Iron Metabolism in Cancer
Cancer cells frequently alter intracellular iron metabolism in a manner that favors iron accumulation: increased iron uptake and storage, decreased iron export, or both. Also, increased iron accumulation is characteristic of tumor-initiating cells and cancer stem cells.
Iron and Cancer[1].
Iron Metabolic Pathways as Potential Cancer Therapeutic Targets
Due to the critical role of iron in cancer, targeting iron metabolism has emerged as a novel therapeutic strategy for the treatment of cancer.
- Iron Chelator
Iron chelators can limit the amount of iron available in tumor cells. Chelators and other drugs can be delivered via TfR1-mediated drug delivery. - Targeted TfR1
Inhibition of TfR1 by antibodies and gene silencing reduces iron input and deprives cells of the required amount of iron. - Targeted HIF
Inhibition of HIF and its target genes ultimately limits the amount of iron available to cells and impedes the ability of cancer cells to proliferate. - Antioxidant Defense Inhibition
Inhibition of cellular antioxidant defenses, such as system XC- and GPX4 predisposes cells to accumulation of ROS due to iron metabolism, leading to lipid peroxidation and iron death.
Potential therapeutic pathways in cancer
targeting abnormal iron metabolism [2].
The key to fighting cancer is to find better treatments, which requires a deep understanding of the underlying biology of the disease at the cellular and molecular level. Protheragen has many years of research experience in the field of iron metabolism studies in cells and individuals and is committed to providing the widest range of tools of the highest quality for oncology research. If you are interested in the services we offer, please contact us for more information.
References
- Wang Y, et al. Iron metabolism in cancer[J]. International journal of molecular sciences, 2018, 20(1): 95.
- Zhang J, et al. Therapeutic potential of iron chelators on osteoporosis and their cellular mechanisms[J]. Biomedicine & Pharmacotherapy, 2021, 137: 111380