Journal
CANCER LETTERS
Volume 467, Issue -, Pages 29-39Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.09.011
Keywords
Cancer metabolism; Combination therapy; Glutaminase isoenzymes; Glutamine; Glutamine synthetase; Synergistic inhibitors
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Funding
- Ministerio de Ciencia, Innovacion y Universidades, Spain [RTI2018-096866-B-I00]
- Ministerio de Ciencia, Innovacion y Universidades [FPU17/04084]
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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.
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