Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Glutaminolysis as a target for cancer therapy

Abstract

Cancer cells display an altered metabolic circuitry that is directly regulated by oncogenic mutations and loss of tumor suppressors. Mounting evidence indicates that altered glutamine metabolism in cancer cells has critical roles in supporting macromolecule biosynthesis, regulating signaling pathways, and maintaining redox homeostasis, all of which contribute to cancer cell proliferation and survival. Thus, intervention in these metabolic processes could provide novel approaches to improve cancer treatment. This review summarizes current findings on the role of glutaminolytic enzymes in human cancers and provides an update on the development of small molecule inhibitors to target glutaminolysis for cancer therapy.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Hsu PP, Sabatini DM . Cancer cell metabolism: Warburg and beyond. Cell 2008; 134: 703–707.

    Article  CAS  PubMed  Google Scholar 

  2. Warburg O . On the origin of cancer cells. Science 1956; 123: 309–314.

    Article  CAS  PubMed  Google Scholar 

  3. Kim JW, Dang CV . Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res 2006; 66: 8927–8930.

    CAS  PubMed  Google Scholar 

  4. Frezza C, Gottlieb E . Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol 2009; 19: 4–11.

    CAS  PubMed  Google Scholar 

  5. Wise DR, Thompson CB . Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci 2010; 35: 427–433.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Medina MA . Glutamine and cancer. J Nutr 2001; 131: 2539S–2542S.

    CAS  PubMed  Google Scholar 

  7. Reitzer LJ, Wice BM, Kennell D . Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 1979; 254: 2669–2676.

    CAS  PubMed  Google Scholar 

  8. Lu W, Pelicano H, Huang P . Cancer metabolism: is glutamine sweeter than glucose? Cancer Cell 2010; 18: 199–200.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 2007; 104: 19345–19350.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wellen KE, Lu C, Mancuso A, Lemons JM, Ryczko M, Dennis JW et al. The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev 2010; 24: 2784–2799.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Duran RV, Oppliger W, Robitaille AM, Heiserich L, Skendaj R, Gottlieb E et al. Glutaminolysis activates Rag-mTORC1 signaling. Mol Cell 2012; 47: 349–358.

    CAS  PubMed  Google Scholar 

  12. Jin L, Li D, Alesi GN, Fan J, Kang HB, Lu Z et al. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth. Cancer Cell 2015; 27: 257–270.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang J, Fan J, Venneti S, Cross JR, Takagi T, Bhinder B et al. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell 2014; 56: 205–218.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Qing G, Li B, Vu A, Skuli N, Walton ZE, Liu X et al. ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 2012; 22: 631–644.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Eng CH, Yu K, Lucas J, White E, Abraham RT . Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci Signal 2010. 3ra31.

  16. Medina MA, Sanchez-Jimenez F, Marquez J, Rodriguez Quesada A, Nunez de Castro I . Relevance of glutamine metabolism to tumor cell growth. Mol Cell Biochem 1992; 113: 1–15.

    CAS  PubMed  Google Scholar 

  17. Kovacevic Z, McGivan JD . Mitochondrial metabolism of glutamine and glutamate and its physiological significance. Physiol Rev 1983; 63: 547–605.

    CAS  PubMed  Google Scholar 

  18. Souba WW . Glutamine and cancer. Ann Surg 1993; 218: 715–728.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. DeBerardinis RJ, Cheng T . Q’s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 2010; 29: 313–324.

    CAS  PubMed  Google Scholar 

  20. Hensley CT, Wasti AT, DeBerardinis RJ . Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest 2013; 123: 3678–3684.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Moreadith RW, Lehninger AL . The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme. J Biol Chem 1984; 259: 6215–6221.

    CAS  PubMed  Google Scholar 

  22. Medina MA, Nunez de Castro I . Glutaminolysis and glycolysis interactions in proliferant cells. Int J Biochem 1990; 22: 681–683.

    CAS  PubMed  Google Scholar 

  23. Dang CV . Glutaminolysis: supplying carbon or nitrogen or both for cancer cells? Cell Cycle 2010; 9: 3884–3886.

    CAS  PubMed  Google Scholar 

  24. McKeehan WL . Glycolysis, glutaminolysis and cell proliferation. Cell Biol Int Rep 1982; 6: 635–650.

    CAS  PubMed  Google Scholar 

  25. Newsholme EA, Crabtree B, Ardawi MS . Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. Q J Exp Physiol 1985; 70: 473–489.

    CAS  PubMed  Google Scholar 

  26. Friday E, Oliver R 3rd, Welbourne T, Turturro F . Glutaminolysis and glycolysis regulation by troglitazone in breast cancer cells: relationship to mitochondrial membrane potential. J Cell Physiol 2011; 226: 511–519.

    CAS  PubMed  Google Scholar 

  27. Mullen AR, Hu Z, Shi X, Jiang L, Boroughs LK, Kovacs Z et al. Oxidation of alpha-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects. Cell Rep 2014; 7: 1679–1690.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012; 481: 380–384.

    CAS  Google Scholar 

  29. Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012; 481: 385–388.

    CAS  Google Scholar 

  30. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 2009; 136: 521–534.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Gorrini C, Harris IS, Mak TW . Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 2013; 12: 931–947.

    CAS  PubMed  Google Scholar 

  32. Harris IS, Treloar AE, Inoue S, Sasaki M, Gorrini C, Lee KC et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell 2015; 27: 211–222.

    CAS  PubMed  Google Scholar 

  33. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009; 458: 762–765.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013; 496: 101–105.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Adam J, Hatipoglu E, O'Flaherty L, Ternette N, Sahgal N, Lockstone H et al. Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell 2011; 20: 524–537.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Ooi A, Wong JC, Petillo D, Roossien D, Perrier-Trudova V, Whitten D et al. An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma. Cancer Cell 2011; 20: 511–523.

    CAS  PubMed  Google Scholar 

  37. Lacey JM, Wilmore DW . Is glutamine a conditionally essential amino acid? Nutr Rev 1990; 48: 297–309.

    CAS  PubMed  Google Scholar 

  38. Bhutia YD, Babu E, Ramachandran S, Ganapathy V . Amino acid transporters in cancer and their relevance to ‘glutamine addiction’: novel targets for the design of a new class of anticancer drugs. Cancer Res 2015; 75: 1782–1788.

    CAS  PubMed  Google Scholar 

  39. Reynolds MR, Lane AN, Robertson B, Kemp S, Liu Y, Hill BG et al. Control of glutamine metabolism by the tumor suppressor Rb. Oncogene 2014; 33: 556–566.

    CAS  PubMed  Google Scholar 

  40. Elorza A, Soro-Arnaiz I, Melendez-Rodriguez F, Rodriguez-Vaello V, Marsboom G, de Carcer G et al. HIF2alpha acts as an mTORC1 activator through the amino acid carrier SLC7A5. Mol Cell 2012; 48: 681–691.

    CAS  PubMed  Google Scholar 

  41. Willems L, Jacque N, Jacquel A, Neveux N, Maciel TT, Lambert M et al. Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia. Blood 2013; 122: 3521–3532.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Hassanein M, Hoeksema MD, Shiota M, Qian J, Harris BK, Chen H et al. SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival. Clin Cancer Res 2013; 19: 560–570.

    CAS  PubMed  Google Scholar 

  43. Hassanein M, Qian J, Hoeksema MD, Wang J, Jacobovitz M, Ji X et al. Targeting SLC1a5-mediated glutamine dependence in non-small cell lung cancer. Int J Cancer 2015; 137: 1587–1597.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang Q, Beaumont KA, Otte NJ, Font J, Bailey CG, van Geldermalsen M et al. Targeting glutamine transport to suppress melanoma cell growth. Int J Cancer 2014; 135: 1060–1071.

    CAS  PubMed  Google Scholar 

  45. Mates JM, Segura JA, Martin-Rufian M, Campos-Sandoval JA, Alonso FJ, Marquez J . Glutaminase isoenzymes as key regulators in metabolic and oxidative stress against cancer. Curr Mol Med 2013; 13: 514–534.

    CAS  PubMed  Google Scholar 

  46. Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ et al. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest 2015; 125: 2293–2306.

    PubMed  PubMed Central  Google Scholar 

  47. Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y . Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol 2007; 178: 93–105.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 2008; 105: 18782–18787.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab 2012; 15: 110–121.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Murphy TA, Dang CV, Young JD . Isotopically nonstationary 13C flux analysis of Myc-induced metabolic reprogramming in B-cells. Metab Eng 2013; 15: 206–217.

    CAS  PubMed  Google Scholar 

  51. Csibi A, Lee G, Yoon SO, Tong H, Ilter D, Elia I et al. The mTORC1/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation. Curr Biol 2014; 24: 2274–2280.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Csibi A, Fendt SM, Li C, Poulogiannis G, Choo AY, Chapski DJ et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 2013; 153: 840–854.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 2010; 18: 207–219.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Thangavelu K, Pan CQ, Karlberg T, Balaji G, Uttamchandani M, Suresh V et al. Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism. Proc Natl Acad Sci USA 2012; 109: 7705–7710.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Colombo SL, Palacios-Callender M, Frakich N, Carcamo S, Kovacs I, Tudzarova S et al. Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc Natl Acad Sci USA 2011; 108: 21069–21074.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Moncada S, Higgs EA, Colombo SL . Fulfilling the metabolic requirements for cell proliferation. Biochem J 2012; 446: 1–7.

    CAS  PubMed  Google Scholar 

  57. Robinson MM, McBryant SJ, Tsukamoto T, Rojas C, Ferraris DV, Hamilton SK et al. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). Biochem J 2007; 406: 407–414.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Gross MI, Demo SD, Dennison JB, Chen L, Chernov-Rogan T, Goyal B et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther 2014; 13: 890–901.

    CAS  PubMed  Google Scholar 

  59. Cheng T, Sudderth J, Yang C, Mullen AR, Jin ES, Mates JM et al. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci USA 2011; 108: 8674–8679.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Tanaka K, Sasayama T, Irino Y, Takata K, Nagashima H, Satoh N et al. Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment. J Clin Invest 2015; 125: 1591–1602.

    PubMed  PubMed Central  Google Scholar 

  61. Herranz D, Ambesi-Impiombato A, Sudderth J, Sanchez-Martin M, Belver L, Tosello V et al. Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia. Nat Med 2015; 21: 1182–1189.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z . Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci USA 2010; 107: 7455–7460.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S et al. Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc Natl Acad Sci USA 2010; 107: 7461–7466.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Martin-Rufian M, Nascimento-Gomes R, Higuero A, Crisma AR, Campos-Sandoval JA, Gomez-Garcia MC et al. Both GLS silencing and GLS2 overexpression synergize with oxidative stress against proliferation of glioma cells. J Mol Med (Berl) 2014; 92: 277–290.

    CAS  Google Scholar 

  65. Xiang L, Xie G, Liu C, Zhou J, Chen J, Yu S et al. Knock-down of glutaminase 2 expression decreases glutathione, NADH, and sensitizes cervical cancer to ionizing radiation. Biochim Biophys Acta 2013; 1833: 2996–3005.

    CAS  PubMed  Google Scholar 

  66. Giacobbe A, Bongiorno-Borbone L, Bernassola F, Terrinoni A, Markert EK, Levine AJ et al. p63 regulates glutaminase 2 expression. Cell Cycle 2013; 12: 1395–1405.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Gao M, Monian P, Quadri N, Ramasamy R, Jiang X . Glutaminolysis and Transferrin regulate Ferroptosis. Mol Cell 2015; 59: 298–308.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Yang C, Sudderth J, Dang T, Bachoo RM, McDonald JG, DeBerardinis RJ . Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res 2009; 69: 7986–7993.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Plaitakis A, Latsoudis H, Spanaki C . The human GLUD2 glutamate dehydrogenase and its regulation in health and disease. Neurochem Int 2011; 59: 495–509.

    CAS  PubMed  Google Scholar 

  70. Smith TJ, Stanley CA . Untangling the glutamate dehydrogenase allosteric nightmare. Trends Biochem Sci 2008; 33: 557–564.

    CAS  PubMed  Google Scholar 

  71. Li C, Allen A, Kwagh J, Doliba NM, Qin W, Najafi H et al. Green tea polyphenols modulate insulin secretion by inhibiting glutamate dehydrogenase. J Biol Chem 2006; 281: 10214–10221.

    CAS  PubMed  Google Scholar 

  72. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 2006; 126: 941–954.

    CAS  PubMed  Google Scholar 

  73. Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med 1998; 338: 1352–1357.

    CAS  PubMed  Google Scholar 

  74. Choo AY, Kim SG, Vander Heiden MG, Mahoney SJ, Vu H, Yoon SO et al. Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol Cell 2010; 38: 487–499.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Lorin S, Tol MJ, Bauvy C, Strijland A, Pous C, Verhoeven AJ et al. Glutamate dehydrogenase contributes to leucine sensing in the regulation of autophagy. Autophagy 2013; 9: 850–860.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Chen R, Nishimura MC, Kharbanda S, Peale F, Deng Y, Daemen A et al. Hominoid-specific enzyme GLUD2 promotes growth of IDH1R132H glioma. Proc Natl Acad Sci USA 2014; 111: 14217–14222.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Yang H, Zhou L, Shi Q, Zhao Y, Lin H, Zhang M et al. SIRT3-dependent GOT2 acetylation status affects the malate-aspartate NADH shuttle activity and pancreatic tumor growth. EMBO J 2015; 34: 1110–1125.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Ahluwalia GS, Grem JL, Hao Z, Cooney DA . Metabolism and action of amino acid analog anti-cancer agents. Pharmacol Ther 1990; 46: 243–271.

    CAS  PubMed  Google Scholar 

  79. Elhammali A, Ippolito JE, Collins L, Crowley J, Marasa J, Piwnica-Worms D . A high-throughput fluorimetric assay for 2-hydroxyglutarate identifies Zaprinast as a glutaminase inhibitor. Cancer Discov 2014; 4: 828–839.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Schulze A, Harris AL . How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 2012; 491: 364–373.

    CAS  PubMed  Google Scholar 

  81. DeLaBarre B, Hurov J, Cianchetta G, Murray S, Dang L . Action at a distance: allostery and the development of drugs to target cancer cell metabolism. Chem Biol 2014; 21: 1143–1161.

    CAS  PubMed  Google Scholar 

  82. Katt WP, Cerione RA . Glutaminase regulation in cancer cells: a druggable chain of events. Drug Discov Today 2014; 19: 450–457.

    CAS  PubMed  Google Scholar 

  83. Shukla K, Ferraris DV, Thomas AG, Stathis M, Duvall B, Delahanty G et al. Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors. J Med Chem 2012; 55: 10551–10563.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Shroff EH, Eberlin LS, Dang VM, Gouw AM, Gabay M, Adam SJ et al. MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci USA 2015; 112: 6539–6544.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Li J, Csibi A, Yang S, Hoffman GR, Li C, Zhang E et al. Synthetic lethality of combined glutaminase and Hsp90 inhibition in mTORC1-driven tumor cells. Proc Natl Acad Sci USA 2015; 112: E21–E29.

    CAS  PubMed  Google Scholar 

  86. Ulanet DB, Couto K, Jha A, Choe S, Wang A, Woo HK et al. Mesenchymal phenotype predisposes lung cancer cells to impaired proliferation and redox stress in response to glutaminase inhibition. PLoS One 2014; 9: e115144.

    PubMed  PubMed Central  Google Scholar 

  87. Katt WP, Ramachandran S, Erickson JW, Cerione RA . Dibenzophenanthridines as inhibitors of glutaminase C and cancer cell proliferation. Mol Cancer Ther 2012; 11: 1269–1278.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Stalnecker CA, Ulrich SM, Li Y, Ramachandran S, McBrayer MK, DeBerardinis RJ et al. Mechanism by which a recently discovered allosteric inhibitor blocks glutamine metabolism in transformed cells. Proc Natl Acad Sci USA 2015; 112: 394–399.

    CAS  PubMed  Google Scholar 

  89. Thornburg JM, Nelson KK, Clem BF, Lane AN, Arumugam S, Simmons A et al. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res 2008; 10: R84.

    PubMed  PubMed Central  Google Scholar 

  90. Korangath P, Teo WW, Sadik H, Han L, Mori N, Huijts CM et al. Targeting glutamine metabolism in breast cancer with aminooxyacetate. Clin Cancer Res 2015; 21: 3263–3273.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Ghesquiere B, Wong BW, Kuchnio A, Carmeliet P . Metabolism of stromal and immune cells in health and disease. Nature 2014; 511: 167–176.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge Dr Anthea Hammond for editorial assistance. We apologize to authors whose contributions were not directly cited in this review due to space limitations. This study is supported in part by ACS grant RSG-11-081-01 and NIH grants R01 CA175316 (S.K.) and F31 CA183365 (G.A.). S.K. is a Georgia Cancer Coalition Scholar, Robbins Scholar, and an American Cancer Society Basic Research Scholar.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to L Jin or S Kang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jin, L., Alesi, G. & Kang, S. Glutaminolysis as a target for cancer therapy. Oncogene 35, 3619–3625 (2016). https://doi.org/10.1038/onc.2015.447

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2015.447

This article is cited by

Search

Quick links