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Glutamine Metabolism in Cancer

  • Chapter
The Heterogeneity of Cancer Metabolism

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1063))

Abstract

Metabolism is the fundamental process for all cellular functions. For decades, there has been growing evidence with regard to the relationship between metabolism and malignant cell proliferation. Unlike normal differentiated cells, however, cancer cells have reprogrammed metabolisms in order to fulfill their energy requirements. These cells display crucial modifications in many metabolic pathways, including glucose transport, glutaminolysis which includes the tricarboxylic acid (TCA) cycle, the electron transport chain (ETC), and the pentose phosphate pathway (PPP) [1]. Since the discovery of the Warburg effect, it has been shown that the metabolism of cancer cells plays a critical role in cancer survival and growth. More recent research suggests that the involvement of glutamine in cancer metabolism is more significant than previously thought. Glutamine, a non essential amino acid with an amine functional group, is the most abundant amino acid circulating in the bloodstream [2]. This chapter will discuss the characteristic features of glutamine metabolism in cancers.

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Abbreviations

α-KG:

α-Ketoglutarate

2HG:

2-Hydroxyglutaric acid

ASS:

Argininosuccinate synthetase

ECG:

Epicatechin gallate

EGCG:

Epigallocatechin gallate

ETC:

Electron transport chain

FDG-PET:

Fluorodeoxyglucose-positron emission tomography

FH:

Fumarate hydratase

GBM:

Glioblastoma multiforme

GDH:

Glutamate dehydrogenase

GLS:

Glutaminase

GOT:

Glutamic-oxaloacetic transaminase

GPT:

Glutamic-pyruvate transaminase

HIF:

Hypoxia-inducible factor

IDH:

Isocitrate dehydrogenase

IDO:

Indoleamine-2,3-dioxygenase

PEG:

Poly(ethylene glycol)

PHD:

Prolyl 4-hydroxylases

PLGA:

Poly(lactic-co-glycolic acid)

PSAT:

Phosphoserine aminotransferase

RCC:

Renal cell carcinomas

SDH:

Succinate dehydrogenase

SHMT:

Serine hydroxymethyltransferase

TCA:

Tricarboxylic acid

TDO:

Tryptophan-2,3-dioxygenase

References

  1. Chen, J. Q., & Russo, J. (2012). Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells. Biochimica et Biophysica Acta, 1826(2), 370–384.

    CAS  PubMed  Google Scholar 

  2. Scriver, C. R., & Rosenberg, L. (1973). Amino acid metabolism and its disorders (Vol. 10). Philadelphia: WB Saunders.

    Google Scholar 

  3. Berg, J. M., Tymoczko, J. L., & Stryer, L. (2012). Biochemistry (7th ed.). New York: W.H. Freeman. xxxii, 1054, 43, 41, 48 p.

    Google Scholar 

  4. Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324(5930), 1029–1033.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Akram, M. (2014). Citric acid cycle and role of its intermediates in metabolism. Cell Biochemistry and Biophysics, 68(3), 475–478.

    Article  CAS  PubMed  Google Scholar 

  6. Cardaci, S., & Ciriolo, M. R. (2012). TCA cycle defects and cancer: When metabolism tunes redox state. Int J Cell Biol, 2012, 161837.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Cairns, R. A., Harris, I. S., & Mak, T. W. (2011). Regulation of cancer cell metabolism. Nature Reviews Cancer, 11(2), 85–95.

    Article  CAS  PubMed  Google Scholar 

  8. Laurenti, G., & Tennant, D. A. (2016). Isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), fumarate hydratase (FH): Three players for one phenotype in cancer? Biochemical Society Transactions, 44(4), 1111–1116.

    Article  CAS  PubMed  Google Scholar 

  9. Bardella, C., Pollard, P. J., & Tomlinson, I. (2011). SDH mutations in cancer. Biochimica et Biophysica Acta, 1807(11), 1432–1443.

    Article  CAS  PubMed  Google Scholar 

  10. Baysal, B. E., et al. (2000). Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science, 287(5454), 848–851.

    Article  CAS  PubMed  Google Scholar 

  11. Baysal, B. E., et al. (2002). Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. Journal of Medical Genetics, 39(3), 178–183.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Burnichon, N., et al. (2010). SDHA is a tumor suppressor gene causing paraganglioma. Human Molecular Genetics, 19(15), 3011–3020.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Ricketts, C., et al. (2008). Germline SDHB mutations and familial renal cell carcinoma. Journal of the National Cancer Institute, 100(17), 1260–1262.

    Article  CAS  PubMed  Google Scholar 

  14. Zantour, B., et al. (2004). A thyroid nodule revealing a paraganglioma in a patient with a new germline mutation in the succinate dehydrogenase B gene. European Journal of Endocrinology, 151(4), 433–438.

    Article  CAS  PubMed  Google Scholar 

  15. Cascon, A., et al. (2008). Molecular characterisation of a common SDHB deletion in paraganglioma patients. Journal of Medical Genetics, 45(4), 233–238.

    Article  CAS  PubMed  Google Scholar 

  16. Tomlinson, I. P., et al. (2002). Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nature Genetics, 30(4), 406–410.

    Article  CAS  PubMed  Google Scholar 

  17. Shanmugasundaram, K., et al. (2014). The oncometabolite fumarate promotes pseudohypoxia through noncanonical activation of NF-kappaB signaling. The Journal of Biological Chemistry, 289(35), 24691–24699.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Dang, L., et al. (2010). Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature, 465(7300), 966.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Parsons, D. W., et al. (2008). An integrated genomic analysis of human glioblastoma multiforme. Science, 321(5897), 1807–1812.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Yan, H., et al. (2009). IDH1 and IDH2 mutations in gliomas. The New England Journal of Medicine, 360(8), 765–773.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Ward, P. S., et al. (2010). The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell, 17(3), 225–234.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Still, E. R., & Yuneva, M. O. (2017). Hopefully devoted to Q: Targeting glutamine addiction in cancer. British Journal of Cancer, 116(11), 1375–1381.

    Article  PubMed  PubMed Central  Google Scholar 

  23. DeBerardinis, R. J., & Cheng, T. (2010). Q’s next: The diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene, 29(3), 313–324.

    Article  CAS  PubMed  Google Scholar 

  24. Mullen, A. R., et al. (2012). Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature, 481(7381), 385–U171.

    Article  CAS  Google Scholar 

  25. Gameiro, P. A., et al. (2013). In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metabolism, 17(3), 372–385.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Dang, L., et al. (2009). Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature, 462(7274), 739–U52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Seltzer, M. J., et al. (2010). Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Research, 70(22), 8981–8987.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Ma, W. W., et al. (2009). [F-18]Fluorodeoxyglucose positron emission tomography correlates with Akt pathway activity but is not predictive of clinical outcome during mTOR inhibitor therapy. Journal of Clinical Oncology, 27(16), 2697–2704.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Ploessl, K., et al. (2012). Comparative evaluation of 18F-labeled glutamic acid and glutamine as tumor metabolic imaging agents. Journal of Nuclear Medicine, 53(10), 1616–1624.

    Article  CAS  PubMed  Google Scholar 

  30. Jeong, S. M., et al. (2016). Enhanced mitochondrial glutamine anaplerosis suppresses pancreatic cancer growth through autophagy inhibition. Scientific Reports, 6, 30767.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Owen, O. E., Kalhan, S. C., & Hanson, R. W. (2002). The key role of anaplerosis and cataplerosis for citric acid cycle function. The Journal of Biological Chemistry, 277(34), 30409–30412.

    Article  PubMed  CAS  Google Scholar 

  32. Umapathy, N. S., et al. (2008). Expression and function of system N glutamine transporters (SN1/SN2 or SNAT3/SNAT5) in retinal ganglion cells. Investigative Ophthalmology & Visual Science, 49(11), 5151–5160.

    Article  Google Scholar 

  33. Wu, G., et al. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489–492.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang, L., et al. (2016). Reactive oxygen species and targeted therapy for pancreatic cancer. Oxidative Medicine and Cellular Longevity, 2016, 1616781.

    PubMed  PubMed Central  Google Scholar 

  35. Elgogary, A., et al. (2016). Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America, 113(36), E5328–E5336.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Le, A., et al. (2012). Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metabolism, 15(1), 110–121.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Erickson, J. W., & Cerione, R. A. (2010). Glutaminase: A hot spot for regulation of cancer cell metabolism? Oncotarget, 1(8), 734–740.

    PubMed  PubMed Central  Google Scholar 

  38. Altman, B. J., Stine, Z. E., & Dang, C. V. (2016). From Krebs to clinic: Glutamine metabolism to cancer therapy. Nature Reviews. Cancer, 16(11), 749.

    Article  CAS  PubMed  Google Scholar 

  39. Colombo, S. L., et al. (2011). Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proceedings of the National Academy of Sciences of the United States of America, 108(52), 21069–21074.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hu, W., et al. (2010). Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proceedings of the National Academy of Sciences of the United States of America, 107(16), 7455–7460.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wise, D. R., et al. (2008). Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proceedings of the National Academy of Sciences of the United States of America, 105(48), 18782–18787.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Gao, P., et al. (2009). c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature, 458(7239), 762–765.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Zilfou, J. T., & Lowe, S. W. (2009). Tumor suppressive functions of p53. Cold Spring Harbor Perspectives in Biology, 1(5), a001883.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Matoba, S., et al. (2006). p53 regulates mitochondrial respiration. Science, 312(5780), 1650–1653.

    Article  CAS  PubMed  Google Scholar 

  45. Sablina, A. A., et al. (2005). The antioxidant function of the p53 tumor suppressor. Nature Medicine, 11(12), 1306–1313.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Wang, J. B., et al. (2010). Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell, 18(4), 397.

    Article  CAS  Google Scholar 

  47. Wang, J. B., et al. (2010). Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell, 18(3), 207–219.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Robinson, M. M., et al. (2007). Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). The Biochemical Journal, 406(3), 407–414.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Gross, M. I., et al. (2014). Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Molecular Cancer Therapeutics, 13(4), 890–901.

    Article  PubMed  CAS  Google Scholar 

  50. Willis, R. C., & Seegmiller, J. E. (1977). The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast. Journal of Cellular Physiology, 93(3), 375–382.

    Article  CAS  PubMed  Google Scholar 

  51. Elgadi, K. M., et al. (1999). Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing. Physiological Genomics, 1(2), 51–62.

    Article  CAS  PubMed  Google Scholar 

  52. Shukla, K., et al. (2012). Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors. Journal of Medicinal Chemistry, 55(23), 10551–10563.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Niu, Z., et al. (2015). Knockdown of c-Myc inhibits cell proliferation by negatively regulating the Cdk/Rb/E2F pathway in nasopharyngeal carcinoma cells. Acta Biochimica et Biophysica Sinica, 47(3), 183–191.

    Article  CAS  PubMed  Google Scholar 

  54. Zhang, X., Ge, Y. L., & Tian, R. H. (2009). The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo. Cellular & Molecular Biology Letters, 14(2), 305–318.

    Article  CAS  Google Scholar 

  55. Lukey, M. J., Katt, W. P., & Cerione, R. A. (2017). Targeting amino acid metabolism for cancer therapy. Drug Discovery Today, 22(5), 796–804.

    Article  CAS  PubMed  Google Scholar 

  56. Jin, L., Alesi, G. N., & Kang, S. (2016). Glutaminolysis as a target for cancer therapy. Oncogene, 35(28), 3619–3625.

    Article  CAS  PubMed  Google Scholar 

  57. Son, J., et al. (2013). Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature, 496(7443), 101–105.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Li, C., et al. (2006). Green tea polyphenols modulate insulin secretion by inhibiting glutamate dehydrogenase. The Journal of Biological Chemistry, 281(15), 10214–10221.

    Article  CAS  PubMed  Google Scholar 

  59. Li, C., et al. (2011). Green tea polyphenols control dysregulated glutamate dehydrogenase in transgenic mice by hijacking the ADP activation site. The Journal of Biological Chemistry, 286(39), 34164–34174.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Yang, C. S., et al. (2009). Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance. Nature Reviews Cancer, 9(6), 429–439.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Li, M., et al. (2009). Novel inhibitors complexed with glutamate dehydrogenase: Allosteric regulation by control of protein dynamics. Journal of Biological Chemistry, 284(34), 22988–23000.

    Article  CAS  Google Scholar 

  62. Yang, C. D., et al. (2009). Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Research, 69(20), 7986–7993.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Ollenschläger, G., et al. (1988). Asparaginase-induced derangements of glutamine-metabolism - the pathogenetic basis for some drug-related side-effects. European Journal of Clinical Investigation, 18(5), 512–516.

    Article  PubMed  Google Scholar 

  64. Wu, M. C., Arimura, G. K., & Yunis, A. A. (1978). Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase. International Journal of Cancer, 22(6), 728–733.

    Article  CAS  PubMed  Google Scholar 

  65. Lukey, M. J., Wilson, K. F., & Cerione, R. A. (2013). Therapeutic strategies impacting cancer cell glutamine metabolism. Future Medicinal Chemistry, 5(14), 1685–1700.

    Article  PubMed  CAS  Google Scholar 

  66. Grigoryan, R. S., et al. (2004). Changes of amino acid serum levels in pediatric patients with higher-risk acute lymphoblastic leukemia (CCG-1961). In Vivo, 18(2), 107–112.

    CAS  PubMed  Google Scholar 

  67. Nguyen, H. A., Su, Y., & Lavie, A. (2016). Structural insight into substrate selectivity of Erwinia chrysanthemi L-asparaginase. Biochemistry, 55(8), 1246–1253.

    Article  PubMed  CAS  Google Scholar 

  68. Ertel, I. J., et al. (1979). Effective dose of L-asparaginase for induction of remission in previously treated children with acute lymphocytic leukemia: A report from Childrens Cancer Study Group. Cancer Research, 39(10), 3893–3896.

    CAS  PubMed  Google Scholar 

  69. Panosyan, E. H., et al. (2014). Asparagine depletion potentiates the cytotoxic effect of chemotherapy against brain tumors. Molecular Cancer Research, 12(5), 694–702.

    Article  CAS  PubMed  Google Scholar 

  70. Stams, W. A., et al. (2003). Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL. Blood, 101(7), 2743–2747.

    Article  CAS  PubMed  Google Scholar 

  71. Thibault, A., et al. (1994). A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer. Cancer Research, 54(7), 1690–1694.

    CAS  PubMed  Google Scholar 

  72. Darmaun, D., et al. (1998). Phenylbutyrate-induced glutamine depletion in humans: Effect on leucine metabolism. The American Journal of Physiology, 274(5 Pt 1), E801–E807.

    CAS  PubMed  Google Scholar 

  73. Fuchs, B. C., & Bode, B. P. (2005). Amino acid transporters ASCT2 and LAT1 in cancer: Partners in crime? Seminars in Cancer Biology, 15(4), 254–266.

    Article  CAS  PubMed  Google Scholar 

  74. Hassanein, M., et al. (2013). SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival. Clinical Cancer Research, 19(3), 560–570.

    Article  CAS  PubMed  Google Scholar 

  75. Ahluwalia, G. S., et al. (1990). Metabolism and action of amino-acid analog anticancer agents. Pharmacology & Therapeutics, 46(2), 243–271.

    Article  CAS  Google Scholar 

  76. Thangavelu, K., et al. (2014). Structural basis for the active site inhibition mechanism of human kidney-type glutaminase (KGA). Scientific Reports, 4, 3827.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Ortlund, E., et al. (2000). Reactions of Pseudomonas 7A glutaminase-asparaginase with diazo analogues of glutamine and asparagine result in unexpected covalent inhibitions and suggests an unusual catalytic triad Thr-Tyr-Glu. Biochemistry, 39(6), 1199–1204.

    Article  CAS  PubMed  Google Scholar 

  78. Ovejera, A. A., et al. (1979). Efficacy of 6-diazo-5-oxo-L-norleucine and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]-6-diazo-5-oxo-norleucine against experimental tumors in conventional and nude mice. Cancer Research, 39(8), 3220–3224.

    CAS  PubMed  Google Scholar 

  79. Beuster, G., et al. (2011). Inhibition of alanine aminotransferase in silico and in vivo promotes mitochondrial metabolism to impair malignant growth. The Journal of Biological Chemistry, 286(25), 22323–22330.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Thornburg, J. M., et al. (2008). Targeting aspartate aminotransferase in breast cancer. Breast Cancer Research, 10(5), R84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Possemato, R., et al. (2011). Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature, 476(7360), 346–350.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Wu, G., & Morris, S. M., Jr. (1998). Arginine metabolism: Nitric oxide and beyond. The Biochemical Journal, 336(Pt 1), 1–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Kobayashi, E., et al. (2010). Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma. Molecular Cancer Therapeutics, 9(3), 535–544.

    Article  CAS  PubMed  Google Scholar 

  84. Ananieva, E. (2015). Targeting amino acid metabolism in cancer growth and anti-tumor immune response. World Journal of Biological Chemistry, 6(4), 281–289.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Grohmann, U., & Bronte, V. (2010). Control of immune response by amino acid metabolism. Immunological Reviews, 236, 243–264.

    Article  CAS  PubMed  Google Scholar 

  86. Godin-Ethier, J., et al. (2011). Indoleamine 2,3-dioxygenase expression in human cancers: Clinical and immunologic perspectives. Clinical Cancer Research, 17(22), 6985–6991.

    Article  CAS  PubMed  Google Scholar 

  87. Mellor, A. L., & Munn, D. H. (1999). Tryptophan catabolism and T-cell tolerance: Immunosuppression by starvation? Immunology Today, 20(10), 469–473.

    Article  CAS  PubMed  Google Scholar 

  88. Uyttenhove, C., et al. (2003). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nature Medicine, 9(10), 1269–1274.

    Article  CAS  PubMed  Google Scholar 

  89. Ino, K., et al. (2008). Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: Its association with disease progression and survival. Clinical Cancer Research, 14(8), 2310–2317.

    Article  CAS  PubMed  Google Scholar 

  90. Moon, Y. W., et al. (2015). Targeting the indoleamine 2,3-dioxygenase pathway in cancer. Journal for Immunotherapy of Cancer, 3, 51.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Beatty, G. L., et al. (2013). A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clinical Cancer Research, 19(22), 6286–6295.

    Article  CAS  PubMed  Google Scholar 

  92. Soliman, H. H., et al. (2016). A phase I study of indoximod in patients with advanced malignancies. Oncotarget, 7(16), 22928–22938.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Pilotte, L., et al. (2012). Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proceedings of the National Academy of Sciences of the United States of America, 109(7), 2497–2502.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Amelio, I., et al. (2014). Serine and glycine metabolism in cancer. Trends in Biochemical Sciences, 39(4), 191–198.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. DeBerardinis, R. J. (2011). Serine metabolism: Some tumors take the road less traveled. Cell Metabolism, 14(3), 285–286.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Pollari, S., et al. (2011). Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. Breast Cancer Research and Treatment, 125(2), 421–430.

    Article  CAS  PubMed  Google Scholar 

  97. Dang, C. V. (2012). MYC on the path to cancer. Cell, 149(1), 22–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Nikiforov, M. A., et al. (2002). A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism. Molecular and Cellular Biology, 22(16), 5793–5800.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. di Salvo, M. L., et al. (2013). Glycine consumption and mitochondrial serine hydroxymethyltransferase in cancer cells: The heme connection. Medical Hypotheses, 80(5), 633–636.

    Article  CAS  PubMed  Google Scholar 

  100. Jain, M., et al. (2012). Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science, 336(6084), 1040–1044.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Daidone, F., et al. (2011). In silico and in vitro validation of serine hydroxymethyltransferase as a chemotherapeutic target of the antifolate drug pemetrexed. European Journal of Medicinal Chemistry, 46(5), 1616–1621.

    Article  CAS  PubMed  Google Scholar 

  102. Maddocks, O. D., et al. (2013). Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature, 493(7433), 542–546.

    Article  CAS  PubMed  Google Scholar 

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  1. Massachusetts Institute of Technology, Cambridge, MA, USA

    Ting Li

  2. Department of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Anne Le

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    Anne Le MD, HDR

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Li, T., Le, A. (2018). Glutamine Metabolism in Cancer. In: Le, A. (eds) The Heterogeneity of Cancer Metabolism. Advances in Experimental Medicine and Biology, vol 1063. Springer, Cham. https://doi.org/10.1007/978-3-319-77736-8_2

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