将铁代谢、脱铁症和癌症联系起来：有效抗癌治疗干预的新靶点和前景
Linking Iron Metabolism, Ferroptosis, and Cancer: New Targets and Prospects for Effective Anticancer Therapeutic Interventions.
摘要(中文译文)
全球每年因癌症死亡约1000万例，亟需新的抗癌治疗策略，包括针对特定癌症类型和分期的铁代谢紊乱进行靶向治疗。许多肿瘤通过外排铁和上调抗氧化系统来逃避治疗并维持转移潜能，从而导致脂质过氧化和铁死亡性细胞死亡受到抑制。同样，许多肿瘤通过确保铁的持续供应来调控肿瘤微环境（TME）。这涉及免疫细胞的表型调节，包括巨噬细胞、中性粒细胞、调节性T淋巴细胞和自然杀伤细胞，以及成纤维细胞，从而促进免疫逃逸和肿瘤生长。特别是肿瘤相关巨噬细胞（TAMs），其可能占肿瘤总体积的约一半，会逐渐大量负载铁，并可通过磁共振成像（MRI）技术检测到。在铁过载状态下，使用螯合药物去铁胺、地拉罗司，尤其是去铁酮的临床有效铁螯合治疗方案，也可能清除TAMs中过量的铁，并可能降低肿瘤恶性程度。去铁酮还可以清除负载铁的肾癌细胞中过量的铁，并可能预防肾癌转移。去铁酮的抗癌潜力还在其他癌症中得到证实，包括在前列腺癌中去除铁，以及通过抑制乳腺癌中的癌症干细胞发挥作用。许多正在进行的临床试验使用不同药物和实验性制剂来诱导或调节铁死亡，也支持基于铁死亡的治疗策略在特定类别癌症患者中的转化潜力。这些进展凸显了铁死亡作为一种潜在关键代谢脆弱性，与治疗耐药和转移性肿瘤相关。总体而言，铁螯合治疗方法和靶向铁死亡可考虑作为单一疗法或与其他抗癌药物联合使用，并可能改善多种癌症的治疗结局，限制疾病进展和死亡率。
Abstract
New anticancer therapeutic strategies, including targeting of iron dysregulation in affected cancer types and stages, are urgently needed to decrease the associated annual cancer death rate of about 10 million worldwide. Many tumours evade treatment and support metastatic potential by effluxing iron and upregulating antioxidant systems, leading to suppression of lipid peroxidation and ferroptotic cell death. Similarly, many tumours manipulate the tumour microenvironment (TME) by ensuring the continuous supply of iron. This involves phenotypic modulation of immune cells, including macrophages, neutrophils, regulatory T lymphocytes, and natural killer cells, as well as fibroblasts, contributing to immune evasion and tumour growth. In particular, tumour-associated macrophages (TAMs), which may account for about half of the tumour's bulk, become progressively heavily loaded with iron and can be detected by magnetic resonance imaging (MRI) technologies. Clinically effective iron chelation therapy protocols in iron-overloaded conditions using the chelating drugs deferoxamine, deferasirox, and especially deferiprone can also potentially remove excess iron from TAMs and may decrease tumour malignancy. Deferiprone can also remove excess iron from iron-loaded renal cancer cells and potentially prevent metastasis in renal carcinoma. The anticancer potential of deferiprone has also been shown in other cancers, including iron removal in prostate cancer and through cancer stem cell inhibition in breast cancer. Many ongoing clinical trials using different drugs and experimental agents for inducing or modulating ferroptosis also support the translational potential of ferroptosis-based therapeutic strategies in selected categories of cancer patients. These advances highlight ferroptosis as a potential key metabolic vulnerability with relevance for treatment-resistant and metastatic tumours. Overall, iron chelation therapeutic approaches and ferroptosis-targeting may be considered for significant use as monotherapies or in combination with other anticancer drugs and could potentially improve therapeutic outcomes and limit disease progression and mortality in many cancers.
如何引用
AMA
Malamati Kourti, George J Kontoghiorghes. Linking Iron Metabolism, Ferroptosis, and Cancer: New Targets and Prospects for Effective Anticancer Therapeutic Interventions.. Cancers. 2026; doi:10.3390/cancers18091436.
APA
Malamati Kourti, George J Kontoghiorghes (2026). Linking Iron Metabolism, Ferroptosis, and Cancer: New Targets and Prospects for Effective Anticancer Therapeutic Interventions.. Cancers. https://doi.org/10.3390/cancers18091436
GB/T 7714
Malamati Kourti, George J Kontoghiorghes. Linking Iron Metabolism, Ferroptosis, and Cancer: New Targets and Prospects for Effective Anticancer Therapeutic Interventions.[J]. Cancers, 2026 doi:10.3390/cancers18091436.
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