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2000
Volume 25, Issue 5
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Hypoxia, characterized by insufficient oxygen supply to tissues, is a significant factor in tumor growth and resistance to treatment. The hypoxia-inducible factor (HIF) signaling pathway is activated when oxygen levels decline, influencing cell activities and promoting tumor progression. HIF-1α and HIF-2α are the main targets for therapeutic intervention in tumors. Nevertheless, the significance of HIF-2α is often overlooked. This review examines the physiological role of HIF-2α in tumor growth and its involvement in tumor growth. HIFs, composed of hypoxia-responsive α and oxygen-insensitive β subunits, play a crucial role in controlling gene expression in both normal and solid tumor tissues under low oxygen levels. HIF-3α, formerly considered a detrimental modulator of HIF-regulated genes, exerts a transcriptional regulatory role by inhibiting gene expression through competition with HIF-1α and HIF-2α for binding to transcriptional sites in target genes under hypoxia. Recent research indicates that various HIF-3 variants exhibit distinct and potentially contrasting functionalities. Hypoxia often occurs during the initiation and progression of cancer formation. Recent research has discovered that HIF-2α, also known as endothelial PAS domain protein 1, has a significant impact on tumors. HIF-2α is a significant cancer-causing gene and a crucial predictor of prognosis in non-small cell lung cancer. However, due to limited research investigating the relationship between HIF-2α and small-cell lung cancer, it is not possible to reach a definitive conclusion. HIF-2α plays a vital function in cancer by preserving the stemness of cancer cells. This review provides a comprehensive overview of HIF-2 and the role of HIF-3 in various cancer-related processes, as well as its potential as a targeted therapeutic approach.

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Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer
Current Molecular Medicine 25, 513 (2025); https://doi.org/10.2174/0115665240303179240427071748
/content/journals/cmm/10.2174/0115665240303179240427071748
/content/journals/cmm/10.2174/0115665240303179240427071748
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  • Article Type:     Review Article
Keyword(s): cancer; HIF-regulated genes; Hypoxia; hypoxia-inducible factor; therapeutics; tumor microenvironment

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