Hypoxia-driven effects in cancer: Characterization, mechanisms, and therapeutic implications

Rachel Shi, Chengheng Liao, Qing Zhang

Research output: Contribution to journalReview articlepeer-review

Abstract

Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferat-ing and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. The following review summarizes current literature regarding effects of hypoxia on DNA repair, metastasis, epithelial-to-mesenchymal transition, the cancer stem cell phenotype, and therapy resistance. We also discuss mechanisms and pathways, such as HIF signaling, mitochon-drial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes. Finally, novel therapeutics that target the hypoxic tumor microenvironment or interfere with hypoxia-induced pathways are reviewed.

Original languageEnglish (US)
Article number678
Pages (from-to)1-26
Number of pages26
JournalCells
Volume10
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Chemoresistance
  • Hypoxia
  • Hypoxia-inducible factors
  • Metastasis

ASJC Scopus subject areas

  • Medicine(all)

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