Cancer’s craving for sugar: an opportunity for clinical exploitation

  • S. YeluriEmail author
  • B. Madhok
  • K. R. Prasad
  • P. Quirke
  • D. G. Jayne


More than 80 years ago, Otto Warburg described the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions, a process subsequently referred to as the Warburg effect or aerobic glycolysis. The exact molecular mechanisms underlying cancers reliance on glycolysis remains unclear, but is likely a combination of an epigenetic response to the hypoxic tumour environment in combination with direct oncogenic stimulation. The aim of the current manuscript is to review the normal process of glycolysis and highlight the alterations that occur with malignant transformation, to consider the potential advantages of glycolytic respiration for cancer cell survival, and finally to explore areas where altered glucose metabolism can be exploited for clinical benefit.


Glycolysis Warburg phenomenon Cancer bioenergetics Reactive oxygen species (ROS) Mitochondria Oxidative phosphorylation Pyruvate dehydrogenase (PDH) Pyruvate dehydrogenase kinase (PDK) Hypoxia Hypoxia-inducible factor Glycolytic enzymes Lactate dehydrogenase 


Conflict of interest statement

The authors have no disclosures and no conflicts of interest.


  1. Altenberg B, Greulich KO (2004) Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics 84(6):1014–1020. doi: 10.1016/j.ygeno.2004.08.010 PubMedCrossRefGoogle Scholar
  2. Arora KK, Pedersen PL (1988) Functional significance of mitochondrial bound hexokinase in tumor cell metabolism. Evidence for preferential phosphorylation of glucose by intramitochondrially generated ATP. J Biol Chem 263(33):17422–17428PubMedGoogle Scholar
  3. Asaka M, Kimura T, Meguro T, Kato M, Kudo M, Miyazaki T et al (1994) Alteration of aldolase isozymes in serum and tissues of patients with cancer and other diseases. J Clin Lab Anal 8(3):144–148. doi: 10.1002/jcla.1860080306 PubMedCrossRefGoogle Scholar
  4. Atsumi T, Chesney J, Metz C, Leng L, Donnelly S, Makita Z et al (2002) High expression of inducible 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (iPFK-2; PFKFB3) in human cancers. Cancer Res 62(20):5881–5887PubMedGoogle Scholar
  5. Baggetto LG (1992) Deviant energetic metabolism of glycolytic cancer cells. Biochimie 74(11):959–974. doi: 10.1016/0300-9084(92)90016-8 PubMedCrossRefGoogle Scholar
  6. Baumann M, Brand K (1988) Purification and characterization of phosphohexose isomerase from human gastrointestinal carcinoma and its potential relationship to neuroleukin. Cancer Res 48(24 Pt 1):7018–7021PubMedGoogle Scholar
  7. Baumann M, Kappl A, Lang T, Brand K, Siegfried W, Paterok E (1990) The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer. Cancer Invest 8(3–4):351–356. doi: 10.3109/07357909009012053 PubMedCrossRefGoogle Scholar
  8. Blum R, Jacob-Hirsch J, Amariglio N, Rechavi G, Kloog Y (2005) Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor-1alpha, causing glycolysis shutdown and cell death. Cancer Res 65(3):999–1006PubMedGoogle Scholar
  9. Bonnet S, Archer SL, lalunis-Turner J, Haromy A, Beaulieu C, Thompson R et al (2007) A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11(1):37–51. doi: 10.1016/j.ccr.2006.10.020 PubMedCrossRefGoogle Scholar
  10. Briasoulis E, Pavlidis N, Terret C, Bauer J, Fiedler W, Schoffski P et al (2003) Glufosfamide administered using a 1-hour infusion given as first-line treatment for advanced pancreatic cancer. A phase II trial of the EORTC-new drug development group. Eur J Cancer 39(16):2334–2340. doi: 10.1016/S0959-8049(03)00629-4 PubMedCrossRefGoogle Scholar
  11. Busk M, Horsman MR, Kristjansen PE, van der Kogel AJ, Bussink J, Overgaard J (2008) Aerobic glycolysis in cancers: implications for the usability of oxygen-responsive genes and fluorodeoxyglucose-PET as markers of tissue hypoxia. Int J Cancer 122(12):2726–2734. doi: 10.1002/ijc.23449 PubMedCrossRefGoogle Scholar
  12. Castagnetti F, Palandri F, Amabile M, Testoni N, Luatti S, Soverini S et al (2009) Results of high-dose imatinib mesylate in intermediate SOKAL risk chronic myeloid leukemia patients in early chronic phase: a phase II trial of the GIMEMA CML WP. Blood 113(15):3428–3434PubMedCrossRefGoogle Scholar
  13. Catherino WH, Mayers CM, Mantzouris T, Armstrong AY, Linehan WM, Segars JH (2007) Compensatory alterations in energy homeostasis characterized in uterine tumors from hereditary leiomyomatosis and renal cell cancer. Fertil Steril 88(Suppl 4):1039–1048. doi: 10.1016/j.fertnstert.2006.11.198 PubMedCrossRefGoogle Scholar
  14. Chandler JD, Williams ED, Slavin JL, Best JD, Rogers S (2003) Expression and localization of GLUT1 and GLUT12 in prostate carcinoma. Cancer 97(8):2035–2042. doi: 10.1002/cncr.11293 PubMedCrossRefGoogle Scholar
  15. Chen G, Gharib TG, Wang H, Huang CC, Kuick R, Thomas DG et al (2003) Protein profiles associated with survival in lung adenocarcinoma. Proc Natl Acad Sci USA 100(23):13537–13542. doi: 10.1073/pnas.2233850100 PubMedCrossRefGoogle Scholar
  16. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R et al (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184):230–233. doi: 10.1038/nature06734 PubMedCrossRefGoogle Scholar
  17. Coleman MC, Asbury CR, Daniels D, Du J, Aykin-Burns N, Smith BJ et al (2008) 2-Deoxy-d-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer. Free Radic Biol Med 44(3):322–331. doi: 10.1016/j.freeradbiomed.2007.08.032 PubMedCrossRefGoogle Scholar
  18. Coy JF, Dressler D, Wilde J, Schubert P (2005) Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer. Clin Lab (Zaragoza) 51(5–6):257–273Google Scholar
  19. Czernin J, Phelps ME (2002) Positron emission tomography scanning: current and future applications. Annu Rev Med 53:89–112. doi: 10.1146/ PubMedCrossRefGoogle Scholar
  20. Dang CV, Semenza GL (1999) Oncogenic alterations of metabolism. Trends Biochem Sci 24(2):68–72. doi: 10.1016/S0968-0004(98)01344-9 PubMedCrossRefGoogle Scholar
  21. De Lena M, Lorusso V, Latorre A, Fanizza G, Gargano G, Caporusso L et al (2001) Paclitaxel, cisplatin and lonidamine in advanced ovarian cancer. A phase II study. Eur J Cancer 37(3):364–368. doi: 10.1016/S0959-8049(00)00400-7 PubMedCrossRefGoogle Scholar
  22. Denko NC, Fontana LA, Hudson KM, Sutphin PD, Raychaudhuri S, Altman R et al (2003) Investigating hypoxic tumor physiology through gene expression patterns. Oncogene 22(37):5907–5914. doi: 10.1038/sj.onc.1206703 PubMedCrossRefGoogle Scholar
  23. Du XL, Hu H, Lin DC, Xia SH, Shen XM, Zhang Y et al (2007) Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma. J Mol Med 85(8):863–875. doi: 10.1007/s00109-007-0159-4 PubMedCrossRefGoogle Scholar
  24. Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR et al (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64(11):3892–3899. doi: 10.1158/0008-5472.CAN-03-2904 PubMedCrossRefGoogle Scholar
  25. Ewald N, Toepler M, Akinci A, Kloer HU, Bretzel RG, Hardt PD (2005) Pyruvate kinase M2 (tumor M2-PK) as a screening tool for colorectal cancer (CRC). A review of current published data. Z Gastroenterol 43(12):1313–1317. doi: 10.1055/s-2005-858657 PubMedCrossRefGoogle Scholar
  26. Fantin VR, St-Pierre J, Leder P (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9(6):425–434. doi: 10.1016/j.ccr.2006.04.023 PubMedCrossRefGoogle Scholar
  27. Filella X, Molina R, Jo J, Mas E, Ballesta AM (1991) Serum phosphohexose isomerase activities in patients with colorectal cancer. Tumour Biol 12(6):360–367PubMedCrossRefGoogle Scholar
  28. Funasaka T, Haga A, Raz A, Nagase H (2001) Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility. Biochem Biophys Res Commun 285(1):118–128. doi: 10.1006/bbrc.2001.5135 PubMedCrossRefGoogle Scholar
  29. Funasaka T, Haga A, Raz A, Nagase H (2002) Tumor autocrine motility factor induces hyperpermeability of endothelial and mesothelial cells leading to accumulation of ascites fluid. Biochem Biophys Res Commun 293(1):192–200. doi: 10.1016/S0006-291X(02)00202-4 PubMedCrossRefGoogle Scholar
  30. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4(11):891–899. doi: 10.1038/nrc1478 PubMedCrossRefGoogle Scholar
  31. Giaccone G, Smit EF, de Jonge M, Dansin E, Briasoulis E, Ardizzoni A et al (2004) Glufosfamide administered by 1-hour infusion as a second-line treatment for advanced non-small cell lung cancer; a phase II trial of the EORTC-New Drug Development Group. Eur J Cancer 40(5):667–672. doi: 10.1016/j.ejca.2003.10.027 PubMedCrossRefGoogle Scholar
  32. Gillies RJ, Gatenby RA (2007) Adaptive landscapes and emergent phenotypes: why do cancers have high glycolysis? J Bioenerg Biomembr 39(3):251–257. doi: 10.1007/s10863-007-9085-y PubMedCrossRefGoogle Scholar
  33. Gottschalk S, Anderson N, Hainz C, Eckhardt SG, Serkova NJ (2004) Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res 10(19):6661–6668. doi: 10.1158/1078-0432.CCR-04-0039 PubMedCrossRefGoogle Scholar
  34. Gwak GY, Yoon JH, Kim KM, Lee HS, Chung JW, Gores GJ (2005) Hypoxia stimulates proliferation of human hepatoma cells through the induction of hexokinase II expression. J Hepatol 42(3):358–364. doi: 10.1016/j.jhep.2004.11.020 PubMedCrossRefGoogle Scholar
  35. Haber RS, Rathan A, Weiser KR, Pritsker A, Itzkowitz SH, Bodian C et al (1998) GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer 83(1):34–40. doi: 10.1002/(SICI)1097-0142(19980701)83:1<34::AID-CNCR5>3.0.CO;2-E PubMedCrossRefGoogle Scholar
  36. Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D et al (2005) ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8(4):311–321. doi: 10.1016/j.ccr.2005.09.008 PubMedCrossRefGoogle Scholar
  37. Hennipman A, Smits J, van Oirschot B, van Houwelingen JC, Rijksen G, Neyt JP et al (1987) Glycolytic enzymes in breast cancer, benign breast disease and normal breast tissue. Tumour Biol 8(5):251–263PubMedCrossRefGoogle Scholar
  38. Hennipman A, van Oirschot BA, Smits J, Rijksen G, Staal GE (1988) Glycolytic enzyme activities in breast cancer metastases. Tumour Biol 9(5):241–248PubMedCrossRefGoogle Scholar
  39. Huang LJ, Chen SX, Luo WJ, Jiang HH, Zhang PF, Yi H (2006) Proteomic analysis of secreted proteins of non-small cell lung cancer. Ai Zheng 25(11):1361–1367PubMedGoogle Scholar
  40. Iyer NV, Kotch LE, Agani F, Leung SW, Laughner E, Wenger RH et al (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12(2):149–162. doi: 10.1101/gad.12.2.149 PubMedCrossRefGoogle Scholar
  41. Kawamura T, Kusakabe T, Sugino T, Watanabe K, Fukuda T, Nashimoto A et al (2001) Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival. Cancer 92(3):634–641. doi: 10.1002/1097-0142(20010801)92:3<634::AID-CNCR1364>3.0.CO;2-X PubMedCrossRefGoogle Scholar
  42. Kim JW, Zeller KI, Wang Y, Jegga AG, Aronow BJ, O’Donnell KA et al (2004) Evaluation of myc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays. Mol Cell Biol 24(13):5923–5936. doi: 10.1128/MCB.24.13.5923-5936.2004 PubMedCrossRefGoogle Scholar
  43. Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3(3):177–185. doi: 10.1016/j.cmet.2006.02.002 PubMedCrossRefGoogle Scholar
  44. Kim W, Yoon JH, Jeong JM, Cheon GJ, Lee TS, Yang JI et al (2007) Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma. Mol Cancer Ther 6(9):2554–2562. doi: 10.1158/1535-7163.MCT-07-0115 PubMedCrossRefGoogle Scholar
  45. Kole HK, Resnick RJ, Van DM, Racker E (1991) Regulation of 6-phosphofructo-1-kinase activity in ras-transformed rat-1 fibroblasts. Arch Biochem Biophys 286(2):586–590. doi: 10.1016/0003-9861(91)90084-V PubMedCrossRefGoogle Scholar
  46. Kondoh H, Lleonart ME, Gil J, Wang J, Degan P, Peters G et al (2005) Glycolytic enzymes can modulate cellular life span. Cancer Res 65(1):177–185PubMedGoogle Scholar
  47. Koukourakis MI, Giatromanolaki A, Simopoulos C, Polychronidis A, Sivridis E (2005a) Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clin Exp Metastasis 22(1):25–30. doi: 10.1007/s10585-005-2343-7 PubMedCrossRefGoogle Scholar
  48. Koukourakis MI, Giatromanolaki A, Sivridis E, Gatter KC, Harris AL (2005b) Pyruvate dehydrogenase and pyruvate dehydrogenase kinase expression in non small cell lung cancer and tumor-associated stroma. Neoplasia 7(1):1–6. doi: 10.1593/neo.04373 PubMedCrossRefGoogle Scholar
  49. Lay AJ, Jiang XM, Kisker O, Flynn E, Underwood A, Condron R et al (2000) Phosphoglycerate kinase acts in tumour angiogenesis as a disulphide reductase. Nature 408(6814):869–873. doi: 10.1038/35048596 PubMedCrossRefGoogle Scholar
  50. Li C, Xiao Z, Chen Z, Zhang X, Li J, Wu X et al (2006) Proteome analysis of human lung squamous carcinoma. Proteomics 6(2):547–558. doi: 10.1002/pmic.200500256 PubMedCrossRefGoogle Scholar
  51. Lidgren A, Bergh A, Grankvist K, Rasmuson T, Ljungberg B (2008) Glucose transporter-1 expression in renal cell carcinoma and its correlation with hypoxia inducible factor-1alpha. BJU Int 101(4):480–484PubMedGoogle Scholar
  52. Macheda ML, Rogers S, Best JD (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202(3):654–662. doi: 10.1002/jcp.20166 PubMedCrossRefGoogle Scholar
  53. Marin-Hernandez A, Rodriguez-Enriquez S, Vital-Gonzalez PA, Flores-Rodriguez FL, Ias-Silva M, Sosa-Garrocho M et al (2006) Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an over-expressed but strongly product-inhibited hexokinase. FEBS J 273(9):1975–1988. doi: 10.1111/j.1742-4658.2006.05214.x PubMedCrossRefGoogle Scholar
  54. Mathupala SP, Rempel A, Pedersen PL (1995) Glucose catabolism in cancer cells. Isolation, sequence, and activity of the promoter for type II hexokinase. J Biol Chem 270(28):16918–16925. doi: 10.1074/jbc.270.28.16918 PubMedCrossRefGoogle Scholar
  55. Medina RA, Owen GI (2002) Glucose transporters: expression, regulation and cancer. Biol Res 35(1):9–26PubMedGoogle Scholar
  56. Mikuriya K, Kuramitsu Y, Ryozawa S, Fujimoto M, Mori S, Oka M et al (2007) Expression of glycolytic enzymes is increased in pancreatic cancerous tissues as evidenced by proteomic profiling by two-dimensional electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. Int J Oncol 30(4):849–855PubMedGoogle Scholar
  57. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17(8):2530–2540PubMedGoogle Scholar
  58. Mueckler M (1994) Facilitative glucose transporters. Eur J Biochem 219(3):713–725. doi: 10.1111/j.1432-1033.1994.tb18550.x PubMedCrossRefGoogle Scholar
  59. Nistico C, Garufi C, Milella M, D’Ottavio AM, Vaccaro A, Fabi A et al (1999) Weekly epirubicin plus lonidamine in advanced breast carcinoma. Breast Cancer Res Treat 56(3):233–237. doi: 10.1023/A:1006213815195 PubMedCrossRefGoogle Scholar
  60. Ojika T, Imaizumi M, Watanabe H, Abe T, Kato K (1992) An immunohistochemical study on three aldolase isozymes in human lung cancer. Nippon Kyobu Geka Gakkai Zasshi 40(3):382–386PubMedGoogle Scholar
  61. Okar DA, Lange AJ (1999) Fructose-2, 6-bisphosphate and control of carbohydrate metabolism in eukaryotes. Biofactors 10(1):1–14. doi: 10.1002/biof.5520100101 PubMedCrossRefGoogle Scholar
  62. Oudard S, Carpentier A, Banu E, Fauchon F, Celerier D, Poupon MF et al (2003) Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme. J Neurooncol 63(1):81–86. doi: 10.1023/A:1023756707900 PubMedCrossRefGoogle Scholar
  63. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC (2006) HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3(3):187–197. doi: 10.1016/j.cmet.2006.01.012 PubMedCrossRefGoogle Scholar
  64. Pasteur L (1861) Experiences et vues nouvelles sur la nature des fermentations. C R Acad Sci 52:1260–1264Google Scholar
  65. Pastorino JG, Hoek JB, Shulga N (2005) Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res 65(22):10545–10554. doi: 10.1158/0008-5472.CAN-05-1925 PubMedCrossRefGoogle Scholar
  66. Pichler BJ, Wehrl HF, Kolb A, Judenhofer MS (2008) Positron emission tomography/magnetic resonance imaging: the next generation of multimodality imaging? Semin Nucl Med 38(3):199–208. doi: 10.1053/j.semnuclmed.2008.02.001 PubMedCrossRefGoogle Scholar
  67. Plas DR, Thompson CB (2002) Cell metabolism in the regulation of programmed cell death. Trends Endocrinol Metab 13(2):75–78. doi: 10.1016/S1043-2760(01)00528-8 PubMedCrossRefGoogle Scholar
  68. Rho M, Kim J, Jee CD, Lee YM, Lee HE, Kim MA et al (2007) Expression of type 2 hexokinase and mitochondria-related genes in gastric carcinoma tissues and cell lines. Anticancer Res 27(1A):251–258PubMedGoogle Scholar
  69. Ristow M (2006) Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metab Care 9(4):339–345. doi: 10.1097/01.mco.0000232892.43921.98 PubMedCrossRefGoogle Scholar
  70. Robey RB, Hay N (2006) Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 25(34):4683–4696. doi: 10.1038/sj.onc.1209595 PubMedCrossRefGoogle Scholar
  71. Robey IF, Lien AD, Welsh SJ, Baggett BK, Gillies RJ (2005) Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors. Neoplasia 7(4):324–330. doi: 10.1593/neo.04430 PubMedCrossRefGoogle Scholar
  72. Rogers S, Docherty SE, Slavin JL, Henderson MA, Best JD (2003) Differential expression of GLUT12 in breast cancer and normal breast tissue. Cancer Lett 193(2):225–233. doi: 10.1016/S0304-3835(03)00010-7 PubMedCrossRefGoogle Scholar
  73. Schek N, Hall BL, Finn OJ (1988) Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human pancreatic adenocarcinoma. Cancer Res 48(22):6354–6359PubMedGoogle Scholar
  74. Schulz TJ, Thierbach R, Voigt A, Drewes G, Mietzner B, Steinberg P et al (2006) Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited. J Biol Chem 281(2):977–981. doi: 10.1074/jbc.M511064200 PubMedCrossRefGoogle Scholar
  75. Seagroves TN, Ryan HE, Lu H, Wouters BG, Knapp M, Thibault P et al (2001) Transcription factor HIF-1 is a necessary mediator of the Pasteur effect in mammalian cells. Mol Cell Biol 21(10):3436–3444. doi: 10.1128/MCB.21.10.3436-3444.2001 PubMedCrossRefGoogle Scholar
  76. Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732. doi: 10.1038/nrc1187 PubMedCrossRefGoogle Scholar
  77. Silletti S, Watanabe H, Hogan V, Nabi IR, Raz A (1991) Purification of B16-F1 melanoma autocrine motility factor and its receptor. Cancer Res 51(13):3507–3511PubMedGoogle Scholar
  78. Singh D, Banerji AK, Dwarakanath BS, Tripathi RP, Gupta JP, Mathew TL et al (2005) Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme. Strahlenther Onkol 181(8):507–514. doi: 10.1007/s00066-005-1320-z PubMedCrossRefGoogle Scholar
  79. Smith TA, Sharma RI, Thompson AM, Paulin FE (2006) Tumor 18F-FDG incorporation is enhanced by attenuation of P53 function in breast cancer cells in vitro. J Nucl Med 47(9):1525–1530PubMedGoogle Scholar
  80. Stacpoole PW, Gilbert LR, Neiberger RE, Carney PR, Valenstein E, Theriaque DW et al (2008) Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate. Pediatrics 121(5):e1223–e1228. doi: 10.1542/peds.2007-2062 PubMedCrossRefGoogle Scholar
  81. Stetak A, Veress R, Ovadi J, Csermely P, Keri G, Ullrich A (2007) Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res 67(4):1602–1608. doi: 10.1158/0008-5472.CAN-06-2870 PubMedCrossRefGoogle Scholar
  82. Tas F, Aykan F, Alici S, Kaytan E, Aydiner A, Topuz E (2001a) Prognostic factors in pancreatic carcinoma: serum LDH levels predict survival in metastatic disease. Am J Clin Oncol 24(6):547–550. doi: 10.1097/00000421-200112000-00003 PubMedCrossRefGoogle Scholar
  83. Tas F, Aydiner A, Demir C, Topuz E (2001b) Serum lactate dehydrogenase levels at presentation predict outcome of patients with limited-stage small-cell lung cancer. Am J Clin Oncol 24(4):376–378. doi: 10.1097/00000421-200108000-00013 PubMedCrossRefGoogle Scholar
  84. Tian M, Zhang H, Higuchi T, Oriuchi N, Nakasone Y, Takata K et al (2005) Hexokinase-II expression in untreated oral squamous cell carcinoma: comparison with FDG PET imaging. Ann Nucl Med 19(4):335–338. doi: 10.1007/BF02984629 PubMedCrossRefGoogle Scholar
  85. Tokunaga K, Nakamura Y, Sakata K, Fujimori K, Ohkubo M, Sawada K et al (1987) Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. Cancer Res 47(21):5616–5619PubMedGoogle Scholar
  86. Turen S, Ozyar E, Altundag K, Gullu I, Atahan IL (2007) Serum lactate dehydrogenase level is a prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy. Cancer Invest 25(5):315–321. doi: 10.1080/07357900701209103 PubMedCrossRefGoogle Scholar
  87. Unwin RD, Craven RA, Harnden P, Hanrahan S, Totty N, Knowles M et al (2003) Proteomic changes in renal cancer and co-ordinate demonstration of both the glycolytic and mitochondrial aspects of the Warburg effect. Proteomics 3(8):1620–1632. doi: 10.1002/pmic.200300464 PubMedCrossRefGoogle Scholar
  88. van den Bent MJ, Grisold W, Frappaz D, Stupp R, Desir JP, Lesimple T et al (2003) European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme. Ann Oncol 14(12):1732–1734. doi: 10.1093/annonc/mdg491 PubMedCrossRefGoogle Scholar
  89. Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314. doi: 10.1126/science.123.3191.309 PubMedCrossRefGoogle Scholar
  90. Watanabe H, Takehana K, Date M, Shinozaki T, Raz A (1996) Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide. Cancer Res 56(13):2960–2963PubMedGoogle Scholar
  91. Watcharasit P, Thiantanawat A, Satayavivad J (2008) GSK3 promotes arsenite-induced apoptosis via facilitation of mitochondria disruption. J Appl Toxicol 28(4):466–474. doi: 10.1002/jat.1296 PubMedCrossRefGoogle Scholar
  92. Wood IS, Trayhurn P (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89(1):3–9. doi: 10.1079/BJN2002763 PubMedCrossRefGoogle Scholar
  93. Zhang B, Chen JY, Chen DD, Wang GB, Shen P (2004) Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and controls. World J Gastroenterol 10(11):1643–1646PubMedGoogle Scholar
  94. Zhang D, Tai LK, Wong LL, Chiu LL, Sethi SK, Koay ES (2005) Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer. Mol Cell Proteomics 4(11):1686–1696. doi: 10.1074/mcp.M400221-MCP200 PubMedCrossRefGoogle Scholar
  95. Zhu YY, Takashi M, Miyake K, Kato K (1991) An immunochemical and immunohistochemical study of aldolase isozymes in renal cell carcinoma. J Urol 146(2):469–472PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • S. Yeluri
    • 1
    • 2
    Email author
  • B. Madhok
    • 1
    • 2
  • K. R. Prasad
    • 1
    • 2
  • P. Quirke
    • 3
  • D. G. Jayne
    • 1
    • 2
  1. 1.Academic Unit of Medicine, Surgery and AnaesthesiaSt. James’s University HospitalLeedsUK
  2. 2.Leeds Institute of Molecular MedicineUniversity of LeedsLeedsUK
  3. 3.Department of Pathology and Tumour Biology, Leeds Institute of Molecular MedicineUniversity of LeedsLeedsUK

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