The dual role of GPX4 in breast cancer: mechanisms of therapeutic resistance and potential for novel targeted therapies.

IF 4.8 3区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Tingyu Gu, Kun Wang, Xiao Yuan, Haowen Tang, Shouchao Wang, Zhihong Zhao
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引用次数: 0

Abstract

Glutathione peroxidase 4 (GPX4) is a key intracellular antioxidant enzyme that maintains oxidative homeostasis by catalyzing the reduction of lipid peroxides and relies on glutathione-specific inhibition of iron death. In recent years, it has been found that GPX4 exhibits significant aberrant expression in breast cancer (BC) and promotes BC development by regulating tumor cell proliferation, invasion, metastasis, and stem cell properties. More importantly, GPX4 overexpression leads to decreased sensitivity of BC to chemotherapy, radiotherapy, endocrine therapy, immune checkpoint inhibitors, and targeted therapies by inhibiting iron death, attenuating oxidative damage, and activating pro-survival signaling pathways. In this paper, we systematically review the molecular characterization of GPX4 and its cancer-promoting mechanism in BC, focusing on resolving its molecular regulatory network in multimodal therapy resistance. Based on the reversal of drug resistance and synergistic anti-tumor effects demonstrated by GPX4 inhibitors in preclinical studies, iron death induction strategies targeting GPX4 or combining with existing therapies are expected to be a new direction to overcome the bottleneck of drug resistance in BC.

GPX4在乳腺癌中的双重作用:治疗耐药机制和新型靶向治疗的潜力。
谷胱甘肽过氧化物酶4 (GPX4)是一种关键的细胞内抗氧化酶,通过催化脂质过氧化物的减少来维持氧化稳态,并依赖于谷胱甘肽特异性抑制铁死亡。近年来,研究发现GPX4在乳腺癌(breast cancer, BC)中表现出显著的异常表达,并通过调节肿瘤细胞的增殖、侵袭、转移和干细胞特性来促进BC的发展。更重要的是,GPX4过表达通过抑制铁死亡、减轻氧化损伤和激活促生存信号通路,导致BC对化疗、放疗、内分泌治疗、免疫检查点抑制剂和靶向治疗的敏感性降低。本文系统综述了GPX4的分子特征及其在BC中的促癌机制,重点探讨了GPX4在多模式耐药中的分子调控网络。基于GPX4抑制剂在临床前研究中显示的逆转耐药和协同抗肿瘤作用,以GPX4为靶点或联合现有疗法的铁死亡诱导策略有望成为克服BC耐药瓶颈的新方向。
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来源期刊
Cancer gene therapy
Cancer gene therapy 医学-生物工程与应用微生物
CiteScore
10.20
自引率
0.00%
发文量
150
审稿时长
4-8 weeks
期刊介绍: Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.
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