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HIF-1α regulates target genes linked to glycolysis, angiogenesis, invasion, metastasis, immune escape, and drug resistance, collectively worsening patient prognosis. Current HIF-1α–targeting therapeutics remain largely preclinical, motivating deeper understanding of HIF-1α structure, function, regulatory signaling, and strategies to overcome HIF-1α-dependent resistance for future clinical translation.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/hypoxia-inducible-factor-in-breast-cancer-role-and-target-for-breast-cancer-treatment-review/339409/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/hypoxia-inducible-factor-in-breast-cancer-role-and-target-for-breast-cancer-treatment-review/339409.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is hypoxia important in breast cancer progression?","Question",{"text":113,"@type":114},"Breast cancer tumors commonly develop hypoxia due to an imbalance between oxygen consumption and supply. 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Immunol. 15:1370800 .  \ndoi: 10.3389/fimmu.2024.1370800  \nCOPYRIGHT  \n© 2024 Zhi, Chen, Huang, Zhang, Zeng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nHypoxia-inducible factor in breast cancer: role and target for breast cancer treatment  \nShijiao Zhi, Chen Chen, Hanlin Huang, Zhengfu Zhang, Fancai Zeng* and Shujun Zhang*  \nDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China  \nGlobally, 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 . Hypoxiainducible 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-1a and its regulatory pathway. It is anticipated that the future will see the introduction of effective HIF-1a inhibitors into clinical trials, offering new hope for breast cancer patients. Therefore, this review focuses on the structure and function of HIF-1a, its role in advancing breast cancer, and strategies to combat HIF-1a-dependent drug resistance, underlining its therapeutic potential.  \nKEYWORDS  \nbreast cancer, hypoxia-inducible factor, angiogenesis, invasion and metastasis, apoptosis and autophagy, drug resistance  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nZhi et al. 10.3389/fimmu.2024.1370800  \nGRAPHICAL ABSTRACT  \nSchematic overview of HIF-1a regulation in breast cancer. Under normoxic conditions, HIF-1a is unstable with a brief half-life. In hypoxic conditions, the depletion of molecular oxygen during mitochondrial oxidative phosphorylation curtails the catalytic functions of PHD and FIH, limiting HIF-1ahydroxylation and degradation, thereby activating the HIF pathway. Subsequently, HIF-1a is involved in angiogenesis, glucose metabolism, cancer cell invasion and metastasis, and immune escape by regulating the expression of target genes.  \n1 Introduction  \nBreast cancer (BC) is the most common type of malignancy among women and t","cbCaiheX4rdrxVUF","https://ap.wps.com/l/cbCaiheX4rdrxVUF","pdf",7189539,"English","# Introduction\n## Hypoxia and the tumor microenvironment\n## HIF family and HIF-1α in cancer","[{\"question\":\"Why is hypoxia important in breast cancer progression?\",\"answer\":\"Breast cancer tumors commonly develop hypoxia due to an imbalance between oxygen consumption and supply. Hypoxia promotes growth, metastasis, and treatment resistance by regulating hypoxia-related gene expression.\"},{\"question\":\"What role does HIF-1α play in breast cancer?\",\"answer\":\"HIF-1α is overexpressed and activated in breast cancer and controls multiple downstream pathways and target genes. It supports glycolysis, angiogenesis, invasion and metastasis, immune escape, and resistance to several therapies.\"},{\"question\":\"What is the current therapeutic status of HIF-1α inhibitors?\",\"answer\":\"Research on drugs targeting HIF-1α is predominantly in the preclinical phase. The review anticipates that effective inhibitors will enter clinical trials to improve outcomes for breast cancer patients.\"}]","Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment - Review | PDF",1790030096]