Reprogramming of the Tumor in the Hypoxic Niche: The Emerging Concept and Associated Therapeutic Strategies

Trends Pharmacol Sci. 2017 Aug;38(8):669-686. doi: 10.1016/j.tips.2017.05.002. Epub 2017 Jun 12.

Abstract

Hypoxia exerts a profound impact on diverse aspects of cancer biology. Increasing evidence has revealed novel functions of hypoxia in cancer cell epigenomics, epitranscriptomics, metabolism, and intercellular communication, all hotspots of cancer research. Several drugs have been developed to target intratumoral hypoxia and have entered clinical trials to treat refractory tumors. However, direct targeting of hypoxia signaling still has limitations in the clinic with regard to cancer progression and resistance to therapy. Comprehensive understanding of the molecular mechanisms by which hypoxia reshapes tumors and their microenvironment, as well as how tumor cells adapt to and thrive in hypoxic conditions, will therefore continue to be a focus of cancer research and will provide new directions for hypoxic tumor treatment.

Keywords: HIF1α; cancer; epigenetics; exosome; hypoxia; metabolism.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / physiology*
  • Cellular Reprogramming / physiology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Tumor Microenvironment

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit