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Cancer
Cancer cells need more iron, continuously supplied, due to their high growth rates. Anti-cancer iron chelators have been sought for years (Torti, S., Torti, F. Iron and cancer: more ore to be mined. Nat Rev Cancer 13, 342–355 (2013). https://doi.org/10.1038/nrc3495 ). Epidemiological evidence links increased body iron stores to increased cancer risk. High intake of dietary iron is associated with an increased risk for some cancers, particularly colorectal cancer. Hereditary haemochromatosis, a genetic disease that leads to excess iron accumulation, is associated with increased cancer risk.
Iron regulates crucial signaling pathways in tumors, including the hypoxia-inducible factor (HIF) and WNT pathways. The expression of ferroportin, hepcidin, transferrin receptor 1(TFR1), haemochromatosis (HFE) and other genes involved in iron metabolism is linked to the prognosis of patients with breast cancer.
Many types of cancer cells reprogram iron metabolism in ways that result in increased iron uptake. They upregulate proteins that are involved in iron uptake, such as transferrin receptor 1 (TFR1), and decrease the expression of iron efflux proteins, such as ferroportin.
Iron management is a valid target for cancer therapy.
DIBI alone kills breast cancer cell lines in a dose-dependent manner while having a very low cytotoxicity for normal cells.
DIBI acts as a chemosensitizer – greatly enhancing cancer chemotherapeutic agents. DIBI was synergistic with cisplatin, doxorubicin, and cyclophosphamide.
The next steps for IV DIBI in oncology development are extensive animal studies in different cancer xenograft models.