Sun Lin-Lin, Linghu Dong-Li, Hung Mien-Chie
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin 300052, China.
Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University Taichung 404, Taiwan.
Am J Cancer Res. 2021 Dec 15;11(12):5856-5863. eCollection 2021.
Ferroptosis is a recently recognized type of programmed cell death and emerges to play an important role in cancer biology and therapies. This unique form of cell death, characterized by iron-dependent lipid peroxidation, is exquisitely regulated by the cellular metabolic networks such as lipid, iron and amino acid metabolism. The sensitivity to ferroptosis varies among different tumors. Recent evidence reveals that triple-negative breast cancer (TNBC), a highly aggressive disease with limited effective targeted therapies is particularly vulnerable to ferroptosis inducers, suggesting this new form of non-apoptotic cell death as an attractive target for the treatment of the "difficult-to-treat" tumor. Intriguingly, ferroptosis has recently been implicated to be involved in T cell-mediated anti-tumor immunity and affect the efficacy of cancer immunotherapy. Better understanding of this ferroptotic cell death will shed light on the discovery of novel combination therapeutic strategies for cancer treatment. Herein, we provide an overview of the key hallmarks of ferroptosis, use TNBC as a model to characterize the regulation of ferroptosis in cancer, and highlight ferroptosis-modulating combination therapeutic strategies in the context of cancer immunotherapy.
铁死亡是一种最近才被认识的程序性细胞死亡类型，在癌症生物学和治疗中发挥着重要作用。这种独特的细胞死亡形式以铁依赖性脂质过氧化为特征，受到脂质、铁和氨基酸代谢等细胞代谢网络的精确调控。不同肿瘤对铁死亡的敏感性各不相同。最近的证据表明，三阴性乳腺癌（TNBC）是一种侵袭性很强、有效靶向治疗有限的疾病，对铁死亡诱导剂特别敏感，这表明这种新的非凋亡性细胞死亡形式是治疗“难治性”肿瘤的一个有吸引力的靶点。有趣的是，最近有研究表明铁死亡参与了T细胞介导的抗肿瘤免疫，并影响癌症免疫治疗的疗效。更好地理解这种铁死亡性细胞死亡将有助于发现新的癌症联合治疗策略。在此，我们概述了铁死亡的关键特征，以TNBC为模型来描述癌症中铁死亡的调控，并强调在癌症免疫治疗背景下调节铁死亡的联合治疗策略。
