Glutamine Addiction: A New Therapeutic Target in Cancer

By David R. Wise, Craig B. Thompson. TIBS -Trends in Biochemical Sciences. Regular ed, 2010

1,712 citations recorded by the source corpus.

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 acid and in maintaining activation of TOR kinase. Moreover, in many cancer cells, glutamine is the primary mitochondrial substrate and is required to maintain mitochondrial membrane potential and integrity as well as support of the NADPH production needed for redox control and macromolecular synthesis.

Subfields: Biochemistry, Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/387d3df9709c15ecf03958ee53977fdc33c34300

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. Jason W. Locasale
2. Joshua D. Rabinowitz
3. J. Mancias
4. Alec C. Kimmelman
5. C. Der
6. Kirsten L. Bryant

In Cancer Research

1. G. Semenza
2. Ming Tan
3. E. White
4. T. Suda
5. Joshua D. Rabinowitz
6. Y. Zhao
7. W. Zong
8. Jason W. Locasale

In Molecular Biology

1. G. Semenza
2. Alec C. Kimmelman
3. E. White
4. Ming Tan
5. S. Y. Chan
6. Joshua D. Rabinowitz
7. Y. Zhao
8. T. Suda

Citations in the corpus

• Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism (2018, background): “Glutamine is a conditionally essential amino acid in rapidly proliferating cells (Curthoys and Watford, 1995) and a potential target in cancer treatment (DeBerardinis and Cheng, 2010; Cheng et al., 2011; Wise and Thompson, 2010).”
• The Emerging Paradigm of Network Medicine in the Study of Human Disease (2012, background): “90–92 Accordingly, the fine detail of systems-level profiling available in cancer biology 93,94 has allowed for a growing number of network-based studies reporting novel metabolic pathways important in driving cellular transformation and thus identifying crucial metabolic targets for…”
• Mitochondria and Cancer (2016, background): “Alongside altered glucose metabolism, cancer cells also increase uptake and utilization of glutamine for their anabolic needs (Wise and Thompson, 2010).”
• The dynamic nature of autophagy in cancer. (2011, background): “…on glucose metabolism via glycolysis for energy production (Vander Heiden et al. 2009; Levine and PuzioKuter 2010), while tumors with Myc overexpression or activation of Ras have been shown to require glutamine to fuel the TCA cycle (Wise et al. 2008; Weinberg et al. 2010; Wise and Thompson 2010).”
• Metabolic regulation of hematopoietic stem cells in the hypoxic niche. (2011, background): “Glutaminolysis is controlled by c-Myc through a coordinated transcriptional program (Wise and Thompson, 2010; Shanware et al., 2011).”
• Antitumor Activity of the Glutaminase Inhibitor CB-839 in Triple-Negative Breast Cancer (2014, background): “One of the key nutrients that fuels the growth of many cancers is the amino acid glutamine, the most abundant amino acid in plasma (3, 4).”
• Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF (2013, positive): “…likely generate ATP via both glycolysis and oxidative phosphorylation (Colombi et al., 2011; Weinberg et al., 2010), and tumor cells may require mitochondria for functions other than ATP generation, such as fatty acid synthesis and glutaminolysis in some cases (Wise and Thompson, 2010; Dang, 2012).”