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Desferoxamine (DFO)—Mediated iron chelation: Rationale for a novel approach to therapy for brain cancer
Abstract
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.
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Due to serious side effects, the applicability of iron chelators during cancer treatment is hampered.
“Unfortunately, due to serious side effects in several cases, e.g., hearing abnormalities, nephropathy, optic neuropathy, and growth failure in children, their applicability during cancer treatment is hampered [135,139].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [135]
The natural siderophore desferrioxamine (DFO) as well as the synthetic chelator derasirox (DFX) and the thiosemicarbazone Triapine have shown promising anti-cancer activity in clinical trials.
“For instance, the natural siderophore desferrioxamine (DFO, Desferal®) [134,135] as well as the synthetic chelator derasirox (DFX, Exiade), which are clinically employed to treat iron overload due to chronic blood transfusion therapy [134], and the thiosemicarbazone Triapine® [136,137] have shown promising anti-cancer activity in clinical trials [138].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [135]
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Iron as a central player and promising target in cancer progression
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“For instance, the natural siderophore desferrioxamine (DFO, Desferal®) [134,135] as well as the synthetic chelator derasirox (DFX, Exiade), which are clinically employed to treat iron overload due to chronic blood transfusion therapy [134], and the thiosemicarbazone Triapine® [136,137] have shown promising anti-cancer…”
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Metadata
- Authors
- Dayani, P. N., Bishop, M. C., Black, K., & Zeltzer, P. M.
- Affiliations
- Northwestern University (US)
- Southern Arizona VA Health Care System (US)
- Cedars-Sinai Medical Center (US)
- Venue
- Journal of Neuro-Oncology
- Published
- 2004-05
- Volume
- 67
- Issue
- 3
- Pages
- 367-377
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- OpenAlex
- W2045480559
- Cited by
- 114
- References
- 61
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 3 · 2019: 7 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Keywords
- iron chelation, brain cancer, central nervous system tumors, iron homeostasis, oxidative stress, anticancer activity, neuroblastoma, leukemia, hepatocellular carcinoma, bladder cancer, adjuvant chemotherapy, DNA synthesis
- MeSH terms
- Brain Neoplasms, Deferoxamine, Humans, Iron, Iron Chelating Agents
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