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Trends in cancerReview

undefined Mar 2025

A hormetic response model for glutamine stress in cancer.

Abstract

Glutamine metabolism supports the development and progression of many cancers and is considered a therapeutic target. Attempts to inhibit glutamine metabolism have resulted in limited success and have not translated into clinical benefit.

The outcomes of these clinical studies, along with preclinical investigations, suggest that cellular stress responses to glutamine deprivation or targeting may be modeled as a biphasic hormetic response.

By recognizing the multifaceted aspects of glutamine metabolism inhibition within a more comprehensive biological framework, the adoption of this model may guide future fundamental and translational studies.

To achieve clinical efficacy, we posit that as a field we will need to anticipate the hormetic effects of glutamine stress and consider how best to co-target cancer cell adaptive mechanisms.

COI Statement

Declaration of interests The authors declare no competing interests.

References:

  • Encarnación-Rosado J and Kimmelman AC (2021) Harnessing metabolic dependencies in pancreatic cancers. Nat Rev Gastroenterol Hepatol 18, 482–492. 10.1038/s41575-021-00431-7
  • Fan Y et al. (2024) Exploiting the Achilles’ heel of cancer: disrupting glutamine metabolism for effective cancer treatment. Front Pharmacol 15, 1345522. 10.3389/fphar.2024.1345522
  • Cluntun AA et al. (2017) Glutamine Metabolism in Cancer: Understanding the Heterogeneity. Trends Cancer 3, 169–180. 10.1016/j.trecan.2017.01.005
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Article info

Journal issue:

  • Volume: 11
  • Issue: 3

Doi:

10.1016/j.trecan.2024.11.008

More resources:

Elsevier Science

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