Perspectives on hypoxia signaling in tumor stroma

Yuqing Zhang, Morgan Coleman, Rolf A. Brekken

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations


Hypoxia is a well-known characteristic of solid tumors that contributes to tumor progression and metastasis. Oxygen deprivation due to high demand of proliferating cancer cells and standard of care therapies induce hypoxia. Hypoxia signaling, mainly mediated by the hypoxia-inducible transcription factor (HIF) family, results in tumor cell migration, proliferation, metabolic changes, and resistance to therapy. Additionally, the hypoxic tumor microenvironment impacts multiple cellular and non-cellular compartments in the tumor stroma, including disordered tumor vasculature, homeostasis of ECM. Hypoxia also has a multifaceted and often contradictory influence on immune cell function, which contributes to an immunosuppressive environment. Here, we review the important function of HIF in tumor stromal components and summarize current clinical trials targeting hypoxia. We provide an overview of hypoxia signaling in tumor stroma that might help address some of the challenges associated with hypoxia-targeted therapies.

Original languageEnglish (US)
Article number3070
Issue number12
StatePublished - Jun 2 2021


  • HIF
  • Hypoxia
  • Immune microenvironment
  • Tumor stroma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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