Iron chelation: a potential therapeutic strategy in oesophageal cancer

Abstract

Raised intracellular iron has been identified as a potential aetiological factor in the development of several epithelial malignancies, including those of the gastrointestinal tract. The mechanism behind this increase is thought to include disorders of iron uptake and storage. Several iron chelators have been identified as potential anti-tumour agents, with much work undertaken to ascertain the exact mode of action. Despite this, there is little known about the role that these drugs play in the cellular iron metabolism of oesophageal cancer. Consequently, the present study looks to review the relationship of two clinically important iron-chelating agents, deferoxamine and deferasirox, on cellular iron uptake and storage in oesophageal squamous and adenocarcinoma. This provides important evidence for the debate about the role these agents have in the clinical management of such tumours.

Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers

“…Bacterial biosynthesis of siderophores (iron-chelating compounds) was associated with higher EAC risk. While excessive iron may promote carcinogenesis (47) and iron chelation has been considered as a potential EAC therapy (48), iron is an essential trace element with deficiency leading to inflammation (49). Bacterial siderophore synthesis may upset iron homeostasis, and thus might increase EAC risk.…”

Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer

“…Many researchers have indicated that DFO has anti-cancer activity against some types of cancer cells. DFO has potent effects on human neuroblastoma cells, esophageal cancer cells and leukemic by inhibition of proliferation and differentiation [ 134 , 135 , 136 ]. In a clinical study, the overall response rate was 20% for hepatocellular carcinoma with DFO treatment [ 137 ].…”

“…Researches have demonstrated that DFX could reduce cellular viability and proliferation in vitro, including small-cell lung cancer, oesophageal cancer and gastric cancer. Moreover, oral DFX was able to significantly suppress tumor growth in xenograft models [ 136 , 139 , 140 ]. Similar to the mechanism of DFO, DFX inhibits the cell cycle through reducing cellular iron acquisition and intracellular iron levels [ 136 , 139 ].…”

Coordination compounds in cancer: Past, present and perspectives

“…Clinical trials have confirmed that some cancers, as neuroblastoma and leukaemia, are sensitive to DFO therapy while normal tissues are affected only in little extent (Desoize, 2004). Nowadays, iron depletion has been proposed for the treatments of several kinds of cancers and metastatic progression (Kovacevic, 2012;Keeler and Brookes, 2013;Richardson et al, 2013;Torti and Torti, 2013). A triapine derivative, di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) is currently under preclinical evaluation (Lane et al, 2014).…”