Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity

Cancer remains one of the most formidable challenges in modern medicine, due to its complex and dynamic nature, which demands innovative therapeutic approaches. One major challenge to cancer treatment is the tumour microenvironment and in particular tumour hypoxia (low oxygen levels), which contribu...

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Main Author: Brian M Ortmann
Format: Article
Language:English
Published: BMJ Publishing Group 2024-07-01
Series:BMJ Oncology
Online Access:https://bmjoncology.bmj.com/content/3/1/e000154.full
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author Brian M Ortmann
author_facet Brian M Ortmann
author_sort Brian M Ortmann
collection DOAJ
description Cancer remains one of the most formidable challenges in modern medicine, due to its complex and dynamic nature, which demands innovative therapeutic approaches. One major challenge to cancer treatment is the tumour microenvironment and in particular tumour hypoxia (low oxygen levels), which contributes to tumour progression and immune evasion. At the cellular level, this is primarily governed by hypoxia-inducible factor (HIF). HIF is a transcription factor that orchestrates cellular responses to low oxygen levels, driving angiogenesis, metabolic adaptation and immune regulation. HIF’s dysregulation is frequently observed in various cancer types and correlates with increased aggressiveness, metastasis, resistance to therapy and poor patient prognosis. Consequently, understanding the cellular mechanisms underlying HIF activation and its downstream effects has become crucial to developing targeted cancer therapies for improving cancer patient outcomes and represents a key step towards precision medicine.Recent advancements in drug development have led to the emergence of HIF inhibitors, which aim to disrupt HIF-driven processes in cancer providing therapeutic benefit. Here, we provide a review of the molecular mechanisms through which HIF promotes tumour growth and resistance, emphasising the potential clinical benefits of HIF-targeted therapies. This review will discuss the challenges and opportunities associated with translating HIF inhibition into clinical practice, including ongoing clinical trials and future directions in the development of HIF-based cancer treatments.
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spelling doaj-art-a2369741e72645ceb422caff8b036efb2025-01-30T08:45:09ZengBMJ Publishing GroupBMJ Oncology2752-79482024-07-013110.1136/bmjonc-2023-000154Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunityBrian M Ortmann0Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UKCancer remains one of the most formidable challenges in modern medicine, due to its complex and dynamic nature, which demands innovative therapeutic approaches. One major challenge to cancer treatment is the tumour microenvironment and in particular tumour hypoxia (low oxygen levels), which contributes to tumour progression and immune evasion. At the cellular level, this is primarily governed by hypoxia-inducible factor (HIF). HIF is a transcription factor that orchestrates cellular responses to low oxygen levels, driving angiogenesis, metabolic adaptation and immune regulation. HIF’s dysregulation is frequently observed in various cancer types and correlates with increased aggressiveness, metastasis, resistance to therapy and poor patient prognosis. Consequently, understanding the cellular mechanisms underlying HIF activation and its downstream effects has become crucial to developing targeted cancer therapies for improving cancer patient outcomes and represents a key step towards precision medicine.Recent advancements in drug development have led to the emergence of HIF inhibitors, which aim to disrupt HIF-driven processes in cancer providing therapeutic benefit. Here, we provide a review of the molecular mechanisms through which HIF promotes tumour growth and resistance, emphasising the potential clinical benefits of HIF-targeted therapies. This review will discuss the challenges and opportunities associated with translating HIF inhibition into clinical practice, including ongoing clinical trials and future directions in the development of HIF-based cancer treatments.https://bmjoncology.bmj.com/content/3/1/e000154.full
spellingShingle Brian M Ortmann
Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity
BMJ Oncology
title Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity
title_full Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity
title_fullStr Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity
title_full_unstemmed Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity
title_short Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity
title_sort hypoxia inducible factor in cancer from pathway regulation to therapeutic opportunity
url https://bmjoncology.bmj.com/content/3/1/e000154.full
work_keys_str_mv AT brianmortmann hypoxiainduciblefactorincancerfrompathwayregulationtotherapeuticopportunity