Hypoxia-inducible factors: cancer progression and clinical translation

Elizabeth E. Wicks, Gregg L. Semenza

Research output: Contribution to journalReview articlepeer-review


Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that mediate angiogenesis, cancer stem cell specification, cell motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, invasion, and metastasis. In this Review, the mechanisms and consequences of HIF activation in cancer cells are presented. The current status and future prospects of small-molecule HIF inhibitors for use as cancer therapeutics are discussed.

Original languageEnglish (US)
Article numbere159839
JournalJournal of Clinical Investigation
Issue number11
StatePublished - Jun 1 2022

ASJC Scopus subject areas

  • Medicine(all)


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