Glutamine addiction: a new therapeutic target in cancer
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Most cancers depend on a high rate of aerobic glycolysis for their continued growth and survival. Paradoxically, some cancer cell lines also display addiction to glutamine despite the fact that glutamine is a nonessential amino acid that can be synthesized from glucose. The high rate of glutamine uptake exhibited by glutamine-dependent cells does not appear to result solely from its role as a nitrogen donor in nucleotide and amino acid biosynthesis. Instead, glutamine plays a required role in the uptake of essential amino acids and in maintaining activation of TOR (target of rapamycin) kinase. Moreover, in many cancer cells, glutamine is the primary mitochondrial substrate and is required for maintenance of mitochondrial membrane potential and integrity and for support of the NADPH production needed for redox control and macromolecular synthesis.
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Glutamine is a key anaplerotic substrate used by cancer cells, providing energy, carbon, and nitrogen to meet the demands of rapid and sustained growth.
“Glutamine (Gln) is a key anaplerotic substrate used by cancer cells, providing energy, carbon, and nitrogen to meet the demands of rapid and sustained growth [7,8].”
From Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer (2020) · cites this paper as [7]
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- Authors
- Wise, D. R., & Thompson, C. B.
- Affiliations
- Abramson Cancer Center (US)
- Corresponding author
- Thompson, Craig B.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 35
- Issue
- 8
- Pages
- 427-433
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC2917518
- OpenAlex
- W2090406819
- Cited by
- 1,770
- References
- 71
- Citations by year
- 2026: 67 · 2025: 113 · 2024: 122 · 2023: 115 · 2022: 144 · 2021: 154 · 2020: 140 · 2019: 159 · 2018: 138 · 2017: 139 · 2016: 133 · 2015: 108 · 2014: 93 · 2013: 64 · 2012: 54
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA105463)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- glutamine addiction, cancer metabolism, glutamine uptake, aerobic glycolysis, TOR kinase, mitochondrial metabolism, mitochondrial membrane potential, NADPH production, redox regulation, therapeutic target
- MeSH terms
- Animals, Glutamine, Humans, Mitochondria, NADP, Neoplasms, Nucleotides, Protein Biosynthesis, TOR Serine-Threonine Kinases, Molecular Targeted Therapy
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