Mo Yuqian, Zou Zhilin, Chen Erbao
School of Public Health, Guangdong Medical University, Zhanjiang, Guangdong, China.
Department of Ophthalmology, Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Hepatol Int. 2024 Feb;18(1):32-49. doi: 10.1007/s12072-023-10593-y. Epub 2023 Oct 26.
Hepatocellular carcinoma (HCC) is a common malignant tumor with complex survival mechanism and drug resistance, resulting in cancer-related high mortality in the world. Ferroptosis represents a form of regulated cell death, typically distinguished by iron-dependent lipid peroxidation. Cancer cells often employ antioxidant defenses to evade the harmful effects of excess iron. Recent research has proposed that directing interventions towards ferroptosis could serve as an effective strategy in curbing the proliferation and invasion of HCC. Immunotherapy has made some preliminary progress in the remodeling of immune microenvironment, but it has not completely inhibited HCC growth, invasion and drug resistance. Furthermore, ferroptosis is widely observed in the formation of immune microenvironment of HCC and mediates the response of many targeted drugs and immunotherapy. Clarifying the role of ferroptosis in these complex processes is expected to provide a new prospect for HCC treatment. In this review, we outline the mechanisms by which HCC develops invasiveness and drug resistance by evading iron-dependent death, and paint a comprehensive landscape of ferroptosis in different cell types in the HCC immune microenvironment.
肝细胞癌(HCC)是一种常见的恶性肿瘤,其生存机制复杂且具有耐药性,导致全球癌症相关死亡率居高不下。铁死亡是一种程序性细胞死亡形式,其典型特征是铁依赖性脂质过氧化。癌细胞常利用抗氧化防御机制来规避过量铁的有害影响。最近的研究表明,针对铁死亡进行干预可能是抑制HCC增殖和侵袭的有效策略。免疫疗法在重塑免疫微环境方面取得了一些初步进展,但尚未完全抑制HCC的生长、侵袭和耐药性。此外,铁死亡在HCC免疫微环境的形成中广泛存在,并介导许多靶向药物和免疫疗法的反应。阐明铁死亡在这些复杂过程中的作用有望为HCC治疗提供新的前景。在这篇综述中,我们概述了HCC通过逃避铁依赖性死亡而产生侵袭性和耐药性的机制,并描绘了HCC免疫微环境中不同细胞类型中铁死亡的全面图景。
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