Abstract
Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.
Highlights
Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide, and its incidence is steadily rising in developing nations [1]
Iron deficiency per se and iron deficiencyinduced hypoxia can trigger the activation of hypoxia-inducible factor (HIF), which are known to mediate cancer progression by upregulating target genes associated with angiogenesis and the metabolic reprogramming of tumor cells [106, 107], causing resistance to chemo- and radiotherapies [108, 109]
IV iron does not appear to have this potential for local exacerbation, as confirmed by rodent studies
Summary
Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide, and its incidence is steadily rising in developing nations [1]. A large number of studies have comprehensively investigated and reviewed the role of excess iron in cancer initiation and progression [5, 9, 10, 12,13,14], potentially tumorigenic effects of iron deficiency have been largely neglected and are not yet well defined [4] This certainly deserves more research, since iron deficiency occurs frequently in patients with CRC, both at the time of diagnosis and throughout the duration of disease [15,16,17]. We investigate the flipside of the coin regarding the role of iron in cancer, addressing consequences of iron deficiency on immune functions key to tumor development and progression, in CRC, and elucidating current options for iron therapy to limit these outcomes
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