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乳腺癌中的缺氧诱导因子:在乳腺癌治疗中的作用和靶点。

Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment.

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China.

出版信息

Front Immunol. 2024 May 10;15:1370800. doi: 10.3389/fimmu.2024.1370800. eCollection 2024.

Abstract

Globally, breast cancer stands as the most prevalent form of cancer among women. The tumor microenvironment of breast cancer often exhibits hypoxia. Hypoxia-inducible factor 1-alpha, a transcription factor, is found to be overexpressed and activated in breast cancer, playing a pivotal role in the anoxic microenvironment by mediating a series of reactions. Hypoxia-inducible factor 1-alpha is involved in regulating downstream pathways and target genes, which are crucial in hypoxic conditions, including glycolysis, angiogenesis, and metastasis. These processes significantly contribute to breast cancer progression by managing cancer-related activities linked to tumor invasion, metastasis, immune evasion, and drug resistance, resulting in poor prognosis for patients. Consequently, there is a significant interest in Hypoxia-inducible factor 1-alpha as a potential target for cancer therapy. Presently, research on drugs targeting Hypoxia-inducible factor 1-alpha is predominantly in the preclinical phase, highlighting the need for an in-depth understanding of HIF-1α and its regulatory pathway. It is anticipated that the future will see the introduction of effective HIF-1α inhibitors into clinical trials, offering new hope for breast cancer patients. Therefore, this review focuses on the structure and function of HIF-1α, its role in advancing breast cancer, and strategies to combat HIF-1α-dependent drug resistance, underlining its therapeutic potential.

摘要

在全球范围内,乳腺癌是女性最常见的癌症类型。乳腺癌的肿瘤微环境常常存在缺氧现象。缺氧诱导因子 1-α(HIF-1-α)是一种转录因子,在乳腺癌中过度表达和激活,通过介导一系列反应在缺氧微环境中发挥关键作用。HIF-1-α 参与调节下游途径和靶基因,这些基因在缺氧条件下至关重要,包括糖酵解、血管生成和转移。这些过程通过管理与肿瘤侵袭、转移、免疫逃逸和耐药性相关的癌症相关活动,显著促进乳腺癌的进展,导致患者预后不良。因此,HIF-1-α 作为癌症治疗的潜在靶点引起了极大的关注。目前,针对 HIF-1-α 的药物研究主要处于临床前阶段,这突显了深入了解 HIF-1-α 及其调节途径的必要性。预计未来将有有效的 HIF-1-α 抑制剂引入临床试验,为乳腺癌患者带来新的希望。因此,本综述重点关注 HIF-1-α 的结构和功能、它在推进乳腺癌中的作用以及对抗 HIF-1-α 依赖性耐药性的策略,强调其治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a35c/11116789/284456d786e0/fimmu-15-1370800-g001.jpg

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