The Role of Iron Chelation Therapy in Colorectal Cancer: A Systematic Review on Its Mechanisms and Therapeutic Potential

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-07-03 DOI:10.1002/cam4.71019

Gihani Vidanapathirana, Md Sajedul Islam, Sujani Gamage, Alfred K. Lam, Vinod Gopalan

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引用次数: 0

Abstract

Background

Despite significant therapeutic advancements in recent decades, colorectal cancer (CRC) continues to exhibit high rates of mortality and morbidity. Chemoresistance and cancer recurrence remain substantial challenges, underscoring the need for novel treatment approaches. Iron chelation therapy has gained profound interest over the years as a potential cancer treatment, leveraging the increased iron demand by tumors. This review evaluates the effects of iron chelation therapy on CRC progression and the underlying mechanisms.

Method

A comprehensive review of in vivo and in vitro studies was conducted to assess the effectiveness of iron chelation therapy in CRC. The literature search covered PubMed, Scopus, Medline (via Web of Science), and EMBASE between January 1995 and March 2024.

Results

Several in vitro and in vivo studies have investigated the impact of iron chelators, such as deferoxamine, deferasirox, thiosemicarbazone-based chelators, quilamine-based chelators, and other novel compounds on CRC. Natural plant extracts with iron-chelating properties have also been explored as potential treatments. Most studies indicate that iron chelation can inhibit the proliferation of colon cancer cells, though some studies suggest cancer-promoting effects. Mechanistically, iron chelation affects several hallmarks of CRC by modulating histone methylation, upregulating NDRG1, and influencing the Wnt/β-catenin and p53 signaling pathways. However, certain iron chelators may inhibit TRAIL-mediated apoptosis and activate the hypoxia-inducible factor (HIF), potentially accelerating CRC progression.

Conclusion

Future exploration of iron chelation therapy in CRC should focus on extensive in vitro, in vivo, and clinical studies to elucidate the precise mechanisms involved. A deeper understanding of the genetic and cellular alterations induced by iron chelation will enhance the development of effective therapeutic strategies for CRC.

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铁螯合治疗在结直肠癌中的作用：对其机制和治疗潜力的系统综述

尽管近几十年来治疗取得了重大进展，但结直肠癌（CRC）的死亡率和发病率仍然很高。化疗耐药和癌症复发仍然是重大挑战，强调需要新的治疗方法。铁螯合疗法作为一种潜在的癌症治疗方法，利用肿瘤对铁的需求增加，多年来获得了广泛的关注。本文综述了铁螯合治疗对结直肠癌进展的影响及其潜在机制。方法通过对体内和体外研究的综合评价，评价铁螯合治疗结直肠癌的有效性。文献检索涵盖了1995年1月至2024年3月间的PubMed、Scopus、Medline（通过Web of Science）和EMBASE。一些体外和体内研究已经探讨了铁螯合剂，如去铁胺、去铁铁、硫代氨基脲螯合剂、奎拉明螯合剂和其他新型化合物对结直肠癌的影响。具有铁螯合特性的天然植物提取物也被视为潜在的治疗方法。大多数研究表明，铁螯合可以抑制结肠癌细胞的增殖，但也有一些研究表明铁具有促癌作用。在机制上，铁螯合通过调节组蛋白甲基化、上调NDRG1和影响Wnt/β-catenin和p53信号通路来影响结直肠癌的几个标志。然而，某些铁螯合剂可能抑制trail介导的细胞凋亡并激活缺氧诱导因子（HIF），可能加速结直肠癌的进展。结论铁螯合治疗结直肠癌的未来探索应集中在广泛的体外、体内和临床研究上，以阐明其确切的机制。对铁螯合引起的遗传和细胞改变的深入了解将促进CRC有效治疗策略的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.