Dysregulation of glutaminase and glutamine synthetase in cancer

  • Cancer Lett. 2019 Dec 28:467:29-39. doi: 10.1016/j.canlet.2019.09.011.
José M Matés  1 ,  José A Campos-Sandoval  2 ,  Juan de Los Santos-Jiménez  2 ,  Javier Márquez  2
Affiliations
  • 1. Department 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. Electronic address: [email protected].
  • 2. Department 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.
PMID: 31574293 DOI: 10.1016/j.canlet.2019.09.011
Abstract

Besides fast glucose catabolism, many types of cancers are characterized by elevated glutamine consumption. Medical oncology pursuits to block specific pathways, mainly glycolysis and glutaminolysis, in tumor cells to arrest Cancer development. This strategy frequently induces adaptive metabolic resistance that must be countered. Combination therapy is an Anticancer synergistic tool to overcome both Cancer growth and resistance mechanisms. Dysregulation of Glutaminase and glutamine synthetase are key events that allow anabolic adaptation of tumors. Several specific drugs that inhibit metabolic Enzymes dealing with glutamine metabolism have been able to eliminate some neoplasms. Targeting the tumor microenvironment can be also another essential factor to be taken into account when single or combined Cancer metabolic therapy fails.

Keywords
Cancer metabolism; Combination therapy; Glutaminase isoenzymes; Glutamine; Glutamine synthetase; Synergistic inhibitors.
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