Desferoxamine (DFO)--mediated iron chelation: rationale for a novel approach to therapy for brain cancer

Iron homeostasis is crucial to normal cell metabolism, and its deficiency or excess is associated with numerous disease states. The association of increased iron load with cancer may be due to several factors including free radical production, reduction of the body's protective mechanism to combat oxidative stress, inhibition of immune systems, inhibition of essential nutrient functions, facilitation of cancer growth, suppression of antitumor actions of macrophages, and lowering of the ratio of T4-T8 positive lymphocytes. Antiproliferative effects of desferoxamine (DFO) both in vitro and in vivo are mediated by an intracellular pool of iron that is necessary for DNA synthesis rather than prevention of iron uptake from transferrin. Several clinical studies have shown it to have antitumor activity in the treatment of neuroblastoma, leukemia, bladder carcinoma, and hepatocellular carcinoma. Human neural tumor cells are susceptible to the effects of DFO. Continued study of DFO is necessary to further elucidate its antineoplastic profile and its use as an adjunct to current chemotherapy regimens. Given the lack of satisfactory treatment of central nervous system neoplasms, DFO could serve as an important tool in the management of such cancers.