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Dysregulation of glutaminase and glutamine synthetase in cancer

José M Matés1, José A Campos-Sandoval1, Juan de Los Santos-Jiménez1

  • 1Department of Molecular Biology and Biochemistry, Canceromics Lab, Faculty of Sciences, Campus de Teatinos, University of Málaga, 29071, Málaga, Spain; Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.

Cancer Letters
|October 2, 2019
PubMed

Insights

Cancer cells consume elevated glutamine, driving tumor growth. Combination therapies targeting glutamine metabolism and the tumor microenvironment are crucial for overcoming cancer resistance.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Biochemistry

Background:

  • Many cancers exhibit rapid glucose breakdown and increased glutamine uptake.
  • Targeting cancer cell metabolism, particularly glycolysis and glutaminolysis, is a key medical oncology strategy.
  • Tumor cells develop adaptive resistance to metabolic inhibitors, necessitating advanced therapeutic approaches.

Purpose of the Study:

  • To explore the role of glutamine metabolism in cancer development and resistance.
  • To evaluate combination therapies for overcoming cancer growth and metabolic resistance.
  • To investigate the potential of targeting glutaminase, glutamine synthetase, and the tumor microenvironment.

Main Methods:

  • Analysis of cancer cell metabolic pathways, focusing on glucose and glutamine.
  • Review of therapeutic strategies involving inhibitors of glutamine metabolism enzymes (glutaminase, glutamine synthetase).
  • Consideration of combination therapies and targeting the tumor microenvironment.

Main Results:

  • Dysregulation of glutaminase and glutamine synthetase facilitates tumor anabolic adaptation.
  • Specific drugs inhibiting glutamine metabolism enzymes have shown efficacy against certain neoplasms.
  • Combination therapy presents a synergistic approach to combat cancer growth and resistance.

Conclusions:

  • Targeting glutamine metabolism is essential for controlling cancer progression.
  • Combination therapies and targeting the tumor microenvironment are vital for overcoming treatment resistance.
  • Further research into metabolic pathway inhibition and combination strategies is warranted.
Keywords:
Cancer metabolismCombination therapyGlutaminase isoenzymesGlutamineGlutamine synthetaseSynergistic inhibitors

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