Hypoxia-Inducible Factors: Master Regulators of Cancer Progression

Luana Schito, Gregg L Semenza

Research output: Contribution to journalReview article


Intratumoral hypoxia (reduced O2 availability) is a common finding in human cancer and leads to increased activity of hypoxia-inducible factors (HIFs), which regulate the expression of genes that contribute to angiogenesis, metabolic reprogramming, extracellular matrix remodeling, epithelial–mesenchymal transition, motility, invasion, metastasis, cancer stem cell maintenance, immune evasion, and resistance to chemotherapy and radiation therapy. Conventional anticancer therapies target well-oxygenated and proliferating cancer cells, whereas there are no approved therapies that target hypoxic cancer cells, despite growing clinical and experimental evidence indicating that intratumoral hypoxia is a critical microenvironmental factor driving cancer progression. In this review, our current understanding of the consequences of HIF activity and the translational potential of targeting HIFs for cancer therapy are discussed.

Original languageEnglish (US)
Pages (from-to)758-770
Number of pages13
JournalTrends in Cancer
Issue number12
Publication statusPublished - Dec 1 2016



  • oxygen biology
  • tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this