HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Ellen C de Heer, Mathilde Jalving, Adrian L Harris*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

133 Citations (Scopus)
173 Downloads (Pure)


Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing of escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in patients with breast cancer. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.

Original languageEnglish
Pages (from-to)5074-5087
Number of pages14
JournalThe Journal of Clinical Investigation
Issue number10
Early online date1-Sept-2020
Publication statusPublished - 1-Oct-2020

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