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HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Ellen C de Heer1, Mathilde Jalving1, Adrian L Harris2

  • 1University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen, Netherlands.

The Journal of Clinical Investigation
|September 2, 2020
PubMed

Insights

Hypoxia-inducible factors (HIFs) drive aggressive breast cancer, but targeting them has proven difficult. Combining therapies, particularly with immunotherapy, shows promise for overcoming resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Hypoxia-inducible factors (HIFs) significantly contribute to breast cancer progression, therapy resistance, and poor patient outcomes.
  • HIF-driven angiogenesis and metabolic reprogramming are critical hallmarks of aggressive breast cancer.

Purpose of the Study:

  • To review the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer.
  • To discuss the challenges and potential strategies for targeting these pathways in breast cancer treatment.

Main Methods:

  • This review synthesizes existing literature on HIFs, angiogenesis, and metabolism in breast cancer.
  • It analyzes the clinical challenges associated with targeting these pathways.
  • It explores potential therapeutic combinations and biomarker development.

Main Results:

  • Targeting HIFs and their downstream effects in breast cancer has faced significant clinical setbacks.
  • Key challenges include selecting appropriate targets, developing predictive biomarkers, and understanding resistance mechanisms.

Conclusions:

  • Despite challenges, targeting HIFs, angiogenesis, and metabolism holds therapeutic potential in breast cancer.
  • Rational combination therapies, especially with immunotherapy and endocrine therapy, are most promising.
  • Further research into the interplay of these factors and the tumor microenvironment is crucial.

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