1 Stupp, R. et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 10, 459–466 (2009).

2 Reya, T., Morrison, S.J., Clarke, M.F. & Weissman, I.L. Stem cells, cancer, and cancer stem cells. Nature 414, 105–111 (2001).

3 Galli, R. et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 64, 7011–7021 (2004).

4 Singh, S.K. et al. Identification of human brain tumour initiating cells. Nature 432, 396–401 (2004).

5 Bao, S. et al. Brain tumor initiating cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756–760 (2006).

6 Liu, G. et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol. Cancer 5, 67 (2006).

7 Warburg, O., Wind, F. & Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol. 8, 519–530 (1927).

8 Peters, A. et al. The selfish brain: competition for energy resources. Neurosci. Biobehav. Rev. 28, 143–180 (2004).

9 Derr, R.L. et al. Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 27, 1082–1086 (2009).

10 Panopoulos, A.D. et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 22, 168–177 (2012).

11 Ward, P.S. & Thompson, C.B. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 21, 297–308 (2012).

12 Li, Z. et al. Hypoxia-inducible factors regulate tumorigenic capacity of brain tumor initiating cells. Cancer Cell 15, 501–513 (2009).

13 Heddleston, J.M., Li, Z., McLendon, R.E., Hjelmeland, A.B. & Rich, J.N. The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle 8, 3274–3284 (2009).

14 Hjelmeland, A.B. et al. Acidic stress promotes a brain tumor initiating cell phenotype. Cell Death Differ. 18, 829–840 (2011).

15 Fellows, L.K. & Boutelle, M.G. Rapid changes in extracellular glucose levels and blood flow in the striatum of the freely moving rat. Brain Res. 604, 225–231 (1993).

16 Burgess, E.A. & Sylven, B. Glucose, lactate, and lactic dehydrogenase activity in normal interstitial fluid and that of solid mouse tumors. Cancer Res. 22, 581–588 (1962).

17 Laks, D.R. et al. Neurosphere formation is an independent predictor of clinical outcome in malignant glioma. Stem Cells 27, 980–987 (2009).

18 Mathews, E.H., Liebenberg, L. & Pelzer, R. High-glycolytic cancers and their interplay with the body's glucose demand and supply cycle. Med. Hypotheses 76, 157–165 (2011).

19 Yoshioka, K. et al. A novel fluorescent derivative of glucose applicable to the assessment of glucose uptake activity of Escherichia coli. Biochim. Biophys. Acta 1289, 5–9 (1996).

20 Song, J. et al. Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature 489, 150–154 (2012).

21 Vannucci, S.J., Maher, F. & Simpson, I.A. Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia 21, 2–21 (1997).

22 Nagamatsu, S., Sawa, H., Wakizaka, A. & Hoshino, T. Expression of facilitative glucose transporter isoforms in human brain tumors. J. Neurochem. 61, 2048–2053 (1993).

23 Boado, R.J., Black, K.L. & Pardridge, W.M. Gene expression of Glut3 and Glut1 glucose transporters in human brain tumors. Brain Res. Mol. Brain Res. 27, 51–57 (1994).

24 Freije, W.A. et al. Gene expression profiling of gliomas strongly predicts survival. Cancer Res. 64, 6503–6510 (2004).

25 Sun, L. et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell 9, 287–300 (2006).

26 Phillips, H.S. et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9, 157–173 (2006).

27 Nutt, C.L. et al. Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res. 63, 1602–1607 (2003).

28 Madhavan, S. et al. Rembrandt: helping personalized medicine become a reality through integrative translational research. Mol. Cancer Res. 7, 157–167 (2009).

29 Cancer Genome Atlas Research Network. Comprehensive genomic characterization define human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008).

30 Verhaak, R.G. et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98–110 (2010).

31 Noushmehr, H. et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17, 510–522 (2010).

32 Turcan, S. et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483, 479–483 (2012).

33 Loncaster, J.A. et al. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res. 61, 6394–6399 (2001).

34 Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).

35 Yu, J. et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797–801 (2009).

36 Younes, M., Lechago, L.V., Somoano, J.R., Mosharaf, M. & Lechago, J. Immunohistochemical detection of Glut3 in human tumors and normal tissues. Anticancer Res. 17, 2747–2750 (1997).

37 Younes, M., Brown, R.W., Stephenson, M., Gondo, M. & Cagle, P.T. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer 80, 1046–1051 (1997).

38 Ayala, F.R. et al. Glut1 and Glut3 as potential prognostic markers for oral squamous cell carcinoma. Molecules 15, 2374–2387 (2010).

39 Baer, S., Casaubon, L., Schwartz, M.R., Marcogliese, A. & Younes, M. Glut3 expression in biopsy specimens of laryngeal carcinoma is associated with poor survival. Laryngoscope 112, 393–396 (2002).

40 Gould, G.W. & Holman, G.D. The glucose transporter family: structure, function and tissue-specific expression. Biochem. J. 295, 329–341 (1993).

41 Charnley, N. et al. No relationship between 18F-fluorodeoxyglucose positron emission tomography and expression of Glut-1 and -3 and hexokinase I and II in high-grade glioma. Oncol. Rep. 20, 537–542 (2008).

42 Chung, J.K. et al. Comparison of [18F]fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-small-cell lung cancer. Nucl. Med. Commun. 25, 11–17 (2004).

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

44 Yan, H. et al. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360, 765–773 (2009).

45 Lu, C. et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483, 474–478 (2012).

46 Rohle, D. et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340, 626–630 (2013).

47 Novakovic, B., Gordon, L., Robinson, W.P., Desoye, G. & Saffery, R. Glucose as a fetal nutrient: dynamic regulation of several glucose transporter genes by DNA methylation in the human placenta across gestation. J. Nutr. Biochem. 24, 282–288 (2013).

48 Chen, Y., Shin, B.C., Thamotharan, S. & Devaskar, S.U. Creb1-Mecp2-(m)CpG complex transactivates postnatal murine neuronal glucose transporter isoform 3 expression. Endocrinology 154, 1598–1611 (2013).

49 Widschwendter, M. et al. Epigenetic stem cell signature in cancer. Nat. Genet. 39, 157–158 (2007).

50 Wong, D.J. et al. Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2, 333–344 (2008).

51 Stoppini, L., Buchs, P.A. & Muller, D. A simple method for organotypic cultures of nervous tissue. J. Neurosci. Methods 37, 173–182 (1991).