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Background <p>Hypoxia, a hallmark of solid tumours, profoundly alters cellular metabolism to enable survival in the harsh tumour microenvironment. Whilst effects on carbohydrate and protein metabolism are well characterised, the hypoxic regulation of lipid metabolism remains poorly understood. Recent advances in lipidomics have revealed that lipids not only serve as energy resources, but have critical roles in oncogenic signalling, cell homeostasis and membrane metabolism. Understanding hypoxia-driven lipid reprogramming could uncover new therapeutic opportunities.</p> Methods <p>A scoping review was conducted following internationally accepted guidelines and reported using the PRISMA-ScR Checklist. MEDLINE, Embase, and Web of Science were searched from inception to 31st August 2025 using tailored strategies, supplemented with grey literature and reference snowballing. Eligible studies included original peer-reviewed research investigating hypoxia and lipid metabolism in cancer using in vitro, in vivo, or human models with physiologically relevant hypoxic conditions. Data were extracted and thematically analysed across four domains: lipid accumulation, lipolysis, membrane metabolism, and lipid signalling.</p> Results <p>From 4632 records identified, 53 studies met the inclusion criteria. Most investigations used immortalised 2D cancer cell lines exposed to chronic, moderate hypoxia (1–2% O₂). Thematic analysis revealed that the majority of studies focused on lipid accumulation, particularly through lipid droplet formation, <i>de novo</i> lipogenesis, and exogenous lipid uptake. Lipolysis, membrane metabolism, and lipid signalling under hypoxic conditions were less frequently examined. Together, these findings highlight a predominant emphasis on lipid storage pathways, with comparatively limited exploration of lipid degradation and signalling processes. A narrative synthesis summarised key mechanisms, identified major knowledge gaps, and outlined emerging therapeutic opportunities in hypoxia-driven lipid metabolism.</p> Conclusions <p>Hypoxia drives diverse, cancer-specific lipidomic adaptations that promote survival and treatment resistance. Although limitations in current models and experimental conditions constrain translation, advancing our understanding of hypoxia-driven lipid reprogramming presents promising avenues for therapeutic development and clinical application.</p>

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The influence of hypoxia on cancer lipid metabolism: a scoping review

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月5日

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  • Henry Douglas Robb,
  • Philip Kwan Hung Leung,
  • Haeun Kim,
  • Daniel Campion-Norman,
  • Bibek Das,
  • Robert Bristow,
  • George Bushra Hanna

摘要

Background

Hypoxia, a hallmark of solid tumours, profoundly alters cellular metabolism to enable survival in the harsh tumour microenvironment. Whilst effects on carbohydrate and protein metabolism are well characterised, the hypoxic regulation of lipid metabolism remains poorly understood. Recent advances in lipidomics have revealed that lipids not only serve as energy resources, but have critical roles in oncogenic signalling, cell homeostasis and membrane metabolism. Understanding hypoxia-driven lipid reprogramming could uncover new therapeutic opportunities.

Methods

A scoping review was conducted following internationally accepted guidelines and reported using the PRISMA-ScR Checklist. MEDLINE, Embase, and Web of Science were searched from inception to 31st August 2025 using tailored strategies, supplemented with grey literature and reference snowballing. Eligible studies included original peer-reviewed research investigating hypoxia and lipid metabolism in cancer using in vitro, in vivo, or human models with physiologically relevant hypoxic conditions. Data were extracted and thematically analysed across four domains: lipid accumulation, lipolysis, membrane metabolism, and lipid signalling.

Results

From 4632 records identified, 53 studies met the inclusion criteria. Most investigations used immortalised 2D cancer cell lines exposed to chronic, moderate hypoxia (1–2% O₂). Thematic analysis revealed that the majority of studies focused on lipid accumulation, particularly through lipid droplet formation, de novo lipogenesis, and exogenous lipid uptake. Lipolysis, membrane metabolism, and lipid signalling under hypoxic conditions were less frequently examined. Together, these findings highlight a predominant emphasis on lipid storage pathways, with comparatively limited exploration of lipid degradation and signalling processes. A narrative synthesis summarised key mechanisms, identified major knowledge gaps, and outlined emerging therapeutic opportunities in hypoxia-driven lipid metabolism.

Conclusions

Hypoxia drives diverse, cancer-specific lipidomic adaptations that promote survival and treatment resistance. Although limitations in current models and experimental conditions constrain translation, advancing our understanding of hypoxia-driven lipid reprogramming presents promising avenues for therapeutic development and clinical application.