Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.

IF 2.7 3区医学 Q2 ONCOLOGY

Clinical & Translational Oncology Pub Date : 2026-10-01 Epub Date: 2026-04-30 DOI:10.1007/s12094-026-04340-6

Honghua Huang, Jintong Na, Jijie Shao, Qun Yang, Jingyi Su, Yupei Xu, Yongxiang Zhao, Liping Zhong

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引用次数: 0

Abstract

Ferroptosis is an iron-dependent form of regulated cell death characterized by excessive lipid peroxidation. Molecules like GPX4, ACSL4, and SLC7A11 form the core regulatory network. GPX4 inhibits lipid peroxide accumulation, ACSL4 promotes ferroptosis through lipid metabolism remodeling, and SLC7A11 confers resistance to ferroptosis by maintaining redox homeostasis. Ferroptosis has a dual role in cancer: inducing it eliminates cancer cells, while its evasion enhances drug resistance and metastasis. Targeting ferroptosis represents an emerging investigational direction for anticancer therapeutic development, with single-target agents, combination regimens, and nanocarrier-based delivery systems exhibiting preliminary tumor-suppressive signals across diverse preclinical model systems. Despite extensive research, existing reviews lack systematic integration of ferroptosis-tumor microenvironment (TME) crosstalk, comparative analysis of cancer type-specific ferroptosis sensitivity, and critical evaluation of recent clinical progress. This review addresses these gaps by synthesizing molecular mechanisms, cancer-specific roles, TME interactions, and therapeutic applications, along with a critical assessment of clinical translation barriers, providing a framework for ferroptosis-targeted cancer therapy.

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癌症中的铁下垂：分子机制、生物学作用和治疗意义。

铁下垂是一种以过度脂质过氧化为特征的铁依赖性细胞死亡形式。GPX4、ACSL4和SLC7A11等分子构成了核心调控网络。GPX4抑制脂质过氧化积累，ACSL4通过脂质代谢重塑促进铁下垂，SLC7A11通过维持氧化还原稳态来抵抗铁下垂。铁下沉在癌症中具有双重作用：诱导它消除癌细胞，而它的逃避则增强了耐药性和转移。靶向铁下垂是抗癌治疗发展的一个新兴研究方向，单靶点药物、联合方案和基于纳米载体的递送系统在不同的临床前模型系统中显示出初步的肿瘤抑制信号。尽管进行了广泛的研究，但现有的综述缺乏对铁下垂-肿瘤微环境（TME）串音的系统整合，对癌症类型特异性铁下垂敏感性的比较分析，以及对近期临床进展的批判性评估。本综述通过合成分子机制、癌症特异性作用、TME相互作用和治疗应用，以及临床翻译障碍的关键评估来解决这些空白，为铁中毒靶向癌症治疗提供一个框架。

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

Clinical & Translational Oncology 医学-肿瘤学

CiteScore

6.20

自引率

2.90%

发文量

240

审稿时长

1 months

期刊介绍： Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.