[en] Diffuse gliomas comprise a group of primary brain tumors that originate from glial (precursor) cells and present as a variety of malignancy grades which have in common that they grow by diffuse infiltration. This phenotype complicates treatment enormously as it precludes curative surgery and radiotherapy. Furthermore, diffusely infiltrating glioma cells often hide behind a functional blood-brain barrier, hampering delivery of systemically administered therapeutic and diagnostic compounds to the tumor cells. The present review addresses the biological mechanisms that underlie the diffuse infiltrative phenotype, knowledge of which may improve treatment strategies for this disastrous tumor type. The invasive phenotype is specific for glioma: most other brain tumor types, both primary and metastatic, grow as delineated lesions. Differences between the genetic make-up of glioma and that of other tumor types may therefore help to unravel molecular pathways, involved in diffuse infiltrative growth. One such difference concerns mutations in the NADP(+)-dependent isocitrate dehydrogenase (IDH1 and IDH2) genes, which occur in >80% of cases of low grade glioma and secondary glioblastoma. In this review we present a novel hypothesis which links IDH1 and IDH2 mutations to glutamate metabolism, possibly explaining the specific biological behavior of diffuse glioma.
Disciplines :
Oncology
Author, co-author :
van Lith, Sanne A M; Radboud University Medical Centre, Department of Pathology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Navis, Anna C; Radboud University Medical Centre, Department of Pathology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Verrijp, Kiek; Radboud University Medical Centre, Department of Pathology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
NICLOU, Simone P. ; Norlux Neuro-Oncology Laboratory, CRP-Santé Luxembourg, Luxembourg
Bjerkvig, Rolf; NorLux Neuro-Oncology, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5019 Bergen, Norway.
Wesseling, Pieter; Radboud University Medical Centre, Department of Pathology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands, Department of Pathology, VU Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Tops, Bastiaan; Radboud University Medical Centre, Department of Pathology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Molenaar, Remco; Department of Cell Biology and Histology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
van Noorden, Cornelis J F; Department of Cell Biology and Histology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Leenders, William P J; Radboud University Medical Centre, Department of Pathology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: william.leenders@radboudumc.nl.
External co-authors :
yes
Language :
English
Title :
Glutamate as chemotactic fuel for diffuse glioma cells: are they glutamate suckers?
Louis D.N., Ohgaki H., Wiestler O.D., Cavenee W.K., Burger P.C., Jouvet A., Scheithauer B.W., Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007, 114:97-109.
Ohgaki H., Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J. Neuropathol. Exp. Neurol. 2005, 64:479-489.
Stummer W., Meinel T., Ewelt C., Martus P., Jakobs O., Felsberg J., Reifenberger G. Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery. J. Neurooncol 2012, 108:89-97.
Ohgaki H., Kleihues P. The definition of primary and secondary glioblastoma. Clin. Cancer Res. 2013, 19:764-772.
Tonjes M., Barbus S., Park Y.J., Wang W., Schlotter M., Lindroth A.M., Pleier S.V., Bai A.H., Karra D., Piro R.M., Felsberg J., Addington A., Lemke D., Weibrecht I., Hovestadt V., Rolli C.G., Campos B., Turcan S., Sturm D., Witt H., Chan T.A., Herold-Mende C., Kemkemer R., Konig R., Schmidt K., Hull W.E., Pfister S.M., Jugold M., Hutson S.M., Plass C., Okun J.G., Reifenberger G., Lichter P., Radlwimmer B. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat. Med. 2013, 19:901-908.
Giese A., Bjerkvig R., Berens M.E., Westphal M. Cost of migration: invasion of malignant gliomas and implications for treatment. J. Clin. Oncol. 2003, 21:1624-1636.
Leenders W., Kusters B., De Waal R. Vessel co-option: how tumors obtain blood supply in the absence of sprouting angiogenesis. Endothelium 2002, 9:83-87.
De Groot J., Sontheimer H. Glutamate and the biology of gliomas. Glia 2011, 59:1181-1189.
De Groot J.F., Liu T.J., Fuller G., Yung W.K. The excitatory amino acid transporter-2 induces apoptosis and decreases glioma growth in vitro and in vivo. Cancer Res. 2005, 65:1934-1940.
Stupp R., Mason W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J., Belanger K., Brandes A.A., Marosi C., Bogdahn U., Curschmann J., Janzer R.C., Ludwin S.K., Gorlia T., Allgeier A., Lacombe D., Cairncross J.G., Eisenhauer E., Mirimanoff R.O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352:987-996.
Gritsenko P.G., Ilina O., Friedl P. Interstitial guidance of cancer invasion. J. Pathol. 2012, 226:185-199.
Claes A., Idema A.J., Wesseling P. Diffuse glioma growth: a guerilla war. Acta Neuropathol. 2007, 114:443-458.
Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
Eisele G., Wick A., Eisele A.C., Clement P.M., Tonn J., Tabatabai G., Ochsenbein A., Schlegel U., Neyns B., Krex D., Simon M., Nikkhah G., Picard M., Stupp R., Wick W., Weller M. Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. J. Neurooncol 2014, 117:141-145..
Barrascout E., Medioni J., Scotte F., Ayllon J., Mejean A., Cuenod C.A., Tartour E., Elaidi R., Oudard S. Angiogenesis inhibition: review of the activity of sorafenib, sunitinib and bevacizumab. Bull. Cancer 2010, 97:29-43.
Gilbert M. RTOG 0825: Phase III Double-blind, Placebo-controlled trial evaluating Bevacizumab in Patients with Newly Diagnosed Glioblastoma, ASCO, Abstract 1 2013.
Hurwitz H., Fehrenbacher L., Novotny W., Cartwright T., Hainsworth J., Heim W., Berlin J., Baron A., Griffing S., Holmgren E., Ferrara N., Fyfe G., Rogers B., Ross R., Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 2004, 350:2335-2342.
Batchelor T.T., Sorensen A.G., di Tomaso E., Zhang W.-T., Duda D.G., Cohen K.S., Kozaki K.R., Cahill D.P., Chen P.-J., Zhu M., Ancukiewicz M., M.M.M., Plotkin S., Drappatz J., Louis D.N., Ivy P., Scadden D.T., Benner T., Loeffier J.S., Wen P.Y., Jain R.K. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007, 11:83-95.
Kamoun W.S., Ley C.D., Farrar C.T., Duyverman A.M., Lahdenranta J., Lacorre D.A., Batchelor T.T., di Tomaso E., Duda D.G., Munn L.L., Fukumura D., Sorensen A.G., Jain R.K. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J. Clin. Oncol. 2009, 27:2542-2552.
Claes A., Gambarota G., Hamans B., van Tellingen O., Wesseling P., Maass C., Heerschap A., Leenders W. Magnetic resonance imaging-based detection of glial brain tumors in mice after antiangiogenic treatment. Int. J. Cancer 2008, 122:1981-1986.
Claes A., Wesseling P., Jeuken J., Maass C., Heerschap A., Leenders W.P. Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization. Mol. Cancer Ther. 2008, 7:71-78.
Navis A.C., Bourgonje A., Wesseling P., Wright A., Hendriks W., Verrijp K., van der Laak J.A., Heerschap A., Leenders W.P. Effects of dual targeting of tumor cells and stroma in human glioblastoma xenografts with a tyrosine kinase inhibitor against c-MET and VEGFR2. PLoS One 2013, 8:e58262.
Navis A.C., Hamans B.C., Claes A., Heerschap A., Jeuken J.W., Wesseling P., Leenders W.P. Effects of targeting the VEGF and PDGF pathways in diffuse orthotopic glioma models. J. Pathol. 2011, 223:626-634.
Mathews M.S., Linskey M.E., Hasso A.N., Fruehauf J.P. The effect of bevacizumab (Avastin) on neuroimaging of brain metastases. Surg. Neurol. 2008, 7:7.
Hamans B., Navis A.C., Wright A., Wesseling P., Heerschap A., Leenders W. Multivoxel 1H MR spectroscopy is superior to contrast-enhanced MRI for response assessment after anti-angiogenic treatment of orthotopic human glioma xenografts and provides handles for metabolic targeting. Neuro Oncol. 2013, 15:1615-1624.
Tabatabai G., Felsberg J., Sabel M., Hofer S., Westphal M., Weller M., Reifenberger G. Bevacizumab failure in glioblastomas. J. Clin. Oncol. 2013, 30. (Suppl. abstract 2067).
Bergers G., Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 2008, 8:592-603.
Leenders W.P., Kusters B., Verrijp K., Maass C., Wesseling P., Heerschap A., Ruiter D., Ryan A., de Waal R. Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin. Cancer Res. 2004, 10:6222-6230.
Wick A., Dorner N., Schafer N., Hofer S., Heiland S., Schemmer D., Platten M., Weller M., Bendszus M., Wick W. Bevacizumab does not increase the risk of remote relapse in malignant glioma. Ann. Neurol. 2011, 69:586-592.
De Groot J.F., Fuller G., Kumar A.J., Piao Y., Eterovic K., Ji Y., Conrad C.A. Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice. Neuro Oncol. 2010, 12:233-242.
Plate K.H., Scholz A., Dumont D.J. Tumor angiogenesis and anti-angiogenic therapy in malignant gliomas revisited. Acta Neuropathol. 2012, 124:763-775.
Gilbert M.R., Dignam J.J., Armstrong T.S., Wefel J.S., Blumenthal D.T., Vogelbaum M.A., Colman H., Chakravarti A., Pugh S., Won M., Jeraj R., Brown P.D., Jaeckle K.A., Schiff D., Stieber V.W., Brachman D.G., Werner-Wasik M., Tremont-Lukats I.W., Sulman E.P., Aldape K.D., Curran W.J., Mehta M.P. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 2014, 370:699-708.
Chinot O.L., Wick W., Mason W., Henriksson R., Saran F., Nishikawa R., Carpentier A.F., Hoang-Xuan K., Kavan P., Cernea D., Brandes A.A., Hilton M., Abrey L., Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N. Engl. J. Med. 2014, 370:709-722.
Verhoeff J.J., van Tellingen O., Claes A., Stalpers L.J., van Linde M.E., Richel D.J., Leenders W.P., van Furth W.R. Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme. BMC Cancer 2009, 9:444.
Gerstner E.R., Duda D.G., di Tomaso E., Ryg P.A., Loeffler J.S., Sorensen A.G., Ivy P., Jain R.K., Batchelor T.T. VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat. Rev. Clin. Oncol. 2009, 6:229-236.
Wen P.Y., Macdonald D.R., Reardon D.A., Cloughesy T.F., Sorensen A.G., Galanis E., Degroot J., Wick W., Gilbert M.R., Lassman A.B., Tsien C., Mikkelsen T., Wong E.T., Chamberlain M.C., Stupp R., Lamborn K.R., Vogelbaum M.A., van den Bent M.J., Chang S.M. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J. Clin. Oncol. 2010, 28:1963-1972.
Ruzinova M.B., Schoer R.A., Gerald W., Egan J.E., Pandolfi P.P., Rafii S., Manova K., Mittal V., Benezra R. Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer Cell 2003, 4:277-289.
Auguste P., Lemiere S., Larrieu-Lahargue F., Bikfalvi A. Molecular mechanisms of tumor vascularization. Crit. Rev. Oncol. Hematol. 2005, 54:53-61.
Keunen O., Johansson M., Oudin A., Sanzey M., Rahim S.A., Fack F., Thorsen F., Taxt T., Bartos M., Jirik R., Miletic H., Wang J., Stieber D., Stuhr L., Moen I., Rygh C.B., Bjerkvig R., Niclou S.P. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:3749-3754.
Endersby R., Baker S.J. PTEN signaling in brain: neuropathology and tumorigenesis. Oncogene 2008, 27:5416-5430.
Nazarenko I., Hede S.M., He X., Hedren A., Thompson J., Lindstrom M.S., Nister M. PDGF and PDGF receptors in glioma. Ups. J. Med. Sci. 2012, 117:99-112.
Raymond E., Brandes A.A., Dittrich C., Fumoleau P., Coudert B., Clement P.M., Frenay M., Rampling R., Stupp R., Kros J.M., Heinrich M.C., Gorlia T., Lacombe D., van den Bent M.J. Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study. J. Clin. Oncol. 2008, 26:4659-4665.
Kong D.S., Song S.Y., Kim D.H., Joo K.M., Yoo J.S., Koh J.S., Dong S.M., Suh Y.L., Lee J.I., Park K., Kim J.H., Nam D.H. Prognostic significance of c-Met expression in glioblastomas. Cancer 2009, 115:140-148.
TheCancerGenomeAtlasResearchNetwork Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008, 455:1061-1068.
Sampson J.H., Archer G.E., Mitchell D.A., Heimberger A.B., Bigner D.D. Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma. Semin. Immunol. 2008, 6:6.
Paugh B.S., Zhu X., Qu C., Endersby R., Diaz A.K., Zhang J., Bax D.A., Carvalho D., Reis R.M., Onar-Thomas A., Broniscer A., Wetmore C., Zhang J., Jones C., Ellison D.W., Baker S.J. Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer Res. 2013, 73:6219-6229.
Klink B., Miletic H., Stieber D., Huszthy P.C., Valenzuela J.A., Balss J., Wang J., Schubert M., Sakariassen P.O., Sundstrom T., Torsvik A., Aarhus M., Mahesparan R., von Deimling A., Kaderali L., Niclou S.P., Schrock E., Bjerkvig R., Nigro J.M. A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1. PLoS One 2013, 8:e59773.
Lo H.W. EGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug resistance. Curr. Mol. Pharmacol. 2010, 3:37-52.
Stupp R., Hegi M.E., Gilbert M.R., Chakravarti A. Chemoradiotherapy in malignant glioma: standard of care and future directions. J. Clin. Oncol. 2007, 25:4127-4136.
Martens T., Laabs Y., Gunther H.S., Kemming D., Zhu Z., Witte L., Hagel C., Westphal M., Lamszus K. Inhibition of glioblastoma growth in a highly invasive nude mouse model can be achieved by targeting epidermal growth factor receptor but not vascular endothelial growth factor receptor-2. Clin. Cancer Res. 2008, 14:5447-5458.
Rahbarizadeh F., Ahmadvand D., Sharifzadeh Z. Nanobody; an old concept and new vehicle for immunotargeting. Immunol. Invest. 2011, 40:299-338.
De Witt Hamer P.C. Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies. Neuro Oncol. 2010, 12:304-316.
Siegal T. Which drug or drug delivery system can change clinical practice for brain tumor therapy?. Neuro Oncol. 2013, 15:656-669.
Parsons D.W., Jones S., Zhang X., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Siu I.M., Gallia G.L., Olivi A., McLendon R., Rasheed B.A., Keir S., Nikolskaya T., Nikolsky Y., Busam D.A., Tekleab H., Diaz L.A., Hartigan J., Smith D.R., Strausberg R.L., Marie S.K., Shinjo S.M., Yan H., Riggins G.J., Bigner D.D., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321:1807-1812.
Yan H., Parsons D.W., Jin G., McLendon R., Rasheed B.A., Yuan W., Kos I., Batinic-Haberle I., Jones S., Riggins G.J., Friedman H., Friedman A., Reardon D., Herndon J., Kinzler K.W., Velculescu V.E., Vogelstein B., Bigner D.D. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 2009, 360:765-773.
Bleeker F.E., Atai N.A., Lamba S., Jonker A., Rijkeboer D., Bosch K.S., Tigchelaar W., Troost D., Vandertop W.P., Bardelli A., Van Noorden C.J. The prognostic IDH1(R132) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma. Acta Neuropathol. 2010, 119:487-494.
Atai N.A., Renkema-Mills N.A., Bosman J., Schmidt N., Rijkeboer D., Tigchelaar W., Bosch K.S., Troost D., Jonker A., Bleeker F.E., Miletic H., Bjerkvig R., De Witt Hamer P.C., Van Noorden C.J. Differential activity of NADPH-producing dehydrogenases renders rodents unsuitable models to study IDH1R132 mutation effects in human glioblastoma. J. Histochem. Cytochem. 2011, 59:489-503.
Bleeker F.E., Lamba S., Leenstra S., Troost D., Hulsebos T., Vandertop W.P., Frattini M., Molinari F., Knowles M., Cerrato A., Rodolfo M., Scarpa A., Felicioni L., Buttitta F., Malatesta S., Marchetti A., Bardelli A. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum. Mutat. 2009, 30:7-11.
Ward P.S., Patel J., Wise D.R., Abdel-Wahab O., Bennett B.D., Coller H.A., Cross J.R., Fantin V.R., Hedvat C.V., Perl A.E., Rabinowitz J.D., Carroll M., Su S.M., Sharp K.A., Levine R.L., Thompson C.B. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010, 17:225-234.
Amary M.F., Bacsi K., Maggiani F., Damato S., Halai D., Berisha F., Pollock R., O'Donnell P., Grigoriadis A., Diss T., Eskandarpour M., Presneau N., Hogendoorn P.C., Futreal A., Tirabosco R., Flanagan A.M. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J. Pathol. 2011, 224:334-343.
Cairns R.A., Mak T.W. Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities. Cancer Discov. 2013, 3:730-741.
Mardis E.R., Ding L., Dooling D.J., Larson D.E., McLellan M.D., Chen K., Koboldt D.C., Fulton R.S., Delehaunty K.D., McGrath S.D., Fulton L.A., Locke D.P., Magrini V.J., Abbott R.M., Vickery T.L., Reed J.S., Robinson J.S., Wylie T., Smith S.M., Carmichael L., Eldred J.M., Harris C.C., Walker J., Peck J.B., Du F., Dukes A.F., Sanderson G.E., Brummett A.M., Clark E., McMichael J.F., Meyer R.J., Schindler J.K., Pohl C.S., Wallis J.W., Shi X., Lin L., Schmidt H., Tang Y., Haipek C., Wiechert M.E., Ivy J.V., Kalicki J., Elliott G., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M.A., Baty J., Heath S., Shannon W.D., Nagarajan R., Link D.C., Walter M.J., Graubert T.A., DiPersio J.F., Wilson R.K., Ley T.J. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 2009, 361:1058-1066.
Yang B., Zhong C., Peng Y., Lai Z., Ding J. Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H. Cell Res. 2010, 20:1188-1200.
Dang L., White D.W., Gross S., Bennett B.D., Bittinger M.A., Driggers E.M., Fantin V.R., Jang H.G., Jin S., Keenan M.C., Marks K.M., Prins R.M., Ward P.S., Yen K.E., Liau L.M., Rabinowitz J.D., Cantley L.C., Thompson C.B., Vander Heiden M.G., Su S.M. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009, 462:739-744.
Borodovsky A., Seltzer M.J., Riggins G.J. Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2. Curr. Opin. Oncol. 2012, 24:83-89.
Xu W., Yang H., Liu Y., Yang Y., Wang P., Kim S.H., Ito S., Yang C., Xiao M.T., Liu L.X., Jiang W.Q., Liu J., Zhang J.Y., Wang B., Frye S., Zhang Y., Xu Y.H., Lei Q.Y., Guan K.L., Zhao S.M., Xiong Y. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 2011, 19:17-30.
Chowdhury R., Yeoh K.K., Tian Y.M., Hillringhaus L., Bagg E.A., Rose N.R., Leung I.K., Li X.S., Woon E.C., Yang M., McDonough M.A., King O.N., Clifton I.J., Klose R.J., Claridge T.D., Ratcliffe P.J., Schofield C.J., Kawamura A. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011, 12:463-469.
Pastor W.A., Aravind L., Rao A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat. Rev. Mol. Cell Biol. 2013, 14:341-356.
Lu C., Ward P.S., Kapoor G.S., Rohle D., Turcan S., Abdel-Wahab O., Edwards C.R., Khanin R., Figueroa M.E., Melnick A., Wellen K.E., O'Rourke D.M., Berger S.L., Chan T.A., Levine R.L., Mellinghoff I.K., Thompson C.B. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 2012, 483:474-478.
Koivunen P., Lee S., Duncan C.G., Lopez G., Lu G., Ramkissoon S., Losman J.A., Joensuu P., Bergmann U., Gross S., Travins J., Weiss S., Looper R., Ligon K.L., Verhaak R.G., Yan H., Kaelin W.G. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 2012, 483:484-488.
Harris A.L. Hypoxia-a key regulatory factor in tumour growth. Nat. Rev. Cancer 2002, 2:38-47.
Rong Y., Durden D.L., Van Meir E.G., Brat D.J. 'Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis. J. Neuropathol. Exp. Neurol. 2006, 65:529-539.
Svensson K.J., Kucharzewska P., Christianson H.C., Skold S., Lofstedt T., Johansson M.C., Morgelin M., Bengzon J., Ruf W., Belting M. Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:13147-13152.
Lai A., Kharbanda S., Pope W.B., Tran A., Solis O.E., Peale F., Forrest W.F., Pujara K., Carrillo J.A., Pandita A., Ellingson B.M., Bowers C.W., Soriano R.H., Schmidt N.O., Mohan S., Yong W.H., Seshagiri S., Modrusan Z., Jiang Z., Aldape K.D., Mischel P.S., Liau L.M., Escovedo C.J., Chen W., Nghiemphu P.L., James C.D., Prados M.D., Westphal M., Lamszus K., Cloughesy T., Phillips H.S. Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. J. Clin. Oncol. 2011, 29:4482-4490.
Losman J.A., Looper R., Koivunen P., Lee S., Schneider R.K., McMahon C., Cowley G., Root D., Ebert B.L., Kaelin W.G. (R)-2-Hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 2013, 339:1621-1625.
Riemenschneider M.J., Reifenberger G. Molecular neuropathology of gliomas. Int. J. Mol. Sci. 2009, 10:184-212.
Lee P., Colman R.F. Implication by site-directed mutagenesis of Arg314 and Tyr316 in the coenzyme site of pig mitochondrial NADP-dependent isocitrate dehydrogenase. Arch. Biochem. Biophys. 2002, 401:81-90.
Reitman Z.J., Jin G., Karoly E.D., Spasojevic I., Yang J., Kinzler K.W., He Y., Bigner D.D., Vogelstein B., Yan H. Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:3270-3275.
Piaskowski S., Bienkowski M., Stoczynska-Fidelus E., Stawski R., Sieruta M., Szybka M., Papierz W., Wolanczyk M., Jaskolski D.J., Liberski P.P., Rieske P. Glioma cells showing IDH1 mutation cannot be propagated in standard cell culture conditions. Br. J. Cancer 2011, 104:968-970.
Luchman H.A., Stechishin O.D., Dang N.H., Blough M.D., Chesnelong C., Kelly J.J., Nguyen S.A., Chan J.A., Weljie A.M., Cairncross J.G., Weiss S. An in vivo patient-derived model of endogenous IDH1-mutant glioma. Neuro Oncol. 2012, 14:184-191.
Navis A.C., Niclou S.P., Fack F., Stieber D., van Lith S., Verrijp K., Wright A., Stauber J., Tops B., Otte-Holler I., Wevers R., van Rooij A., Pusch S., Von Deimling A., Tigchelaar W., Van Noorden C.J., Wesseling P., Leenders W. Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model: in situ detection of 2-HG and α-KG. Acta Neuropathol. Comm. 2013, 1:18.
Jin G., Pirozzi C.J., Chen L.H., Lopez G.Y., Duncan C.G., Feng J., Spasojevic I., Bigner D.D., He Y., Yan H. Mutant IDH1 is required for IDH1 mutated tumor cell growth. Oncotarget 2012, 3:774-782.
Pansuriya T.C., van Eijk R., d'Adamo P., van Ruler M.A., Kuijjer M.L., Oosting J., Cleton-Jansen A.M., van Oosterwijk J.G., Verbeke S.L., Meijer D., van Wezel T., Nord K.H., Sangiorgi L., Toker B., Liegl-Atzwanger B., San-Julian M., Sciot R., Limaye N., Kindblom L.G., Daugaard S., Godfraind C., Boon L.M., Vikkula M., Kurek K.C., Szuhai K., French P.J., Bovee J.V. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat. Genet. 2011, 43:1256-1261.
Sasaki M., Knobbe C.B., Itsumi M., Elia A.J., Harris I.S., Chio I.I., Cairns R.A., McCracken S., Wakeham A., Haight J., Ten A.Y., Snow B., Ueda T., Inoue S., Yamamoto K., Ko M., Rao A., Yen K.E., Su S.M., Mak T.W. D-2-Hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function. Genes Dev. 2012, 26:2038-2049.
Pietrak B., Zhao H., Qi H., Quinn C., Gao E., Boyer J.G., Concha N., Brown K., Duraiswami C., Wooster R., Sweitzer S., Schwartz B. A tale of two subunits: how the neomorphic R132H IDH1 mutation enhances production of alphaHG. Biochemistry 2011, 50:4804-4812.
Baldewpersad Tewarie N.M., Burgers I.A., Dawood Y., den Boon H.C., den Brok M.G., Klunder J.H., Koopmans K.B., Rademaker E., van den Broek H.B., van den Bersselaar S.M., Witjes J.J., Van Noorden C.J., Atai N.A. NADP+-dependent IDH1 R132 mutation and its relevance for glioma patient survival. Med. Hypotheses 2013, 80:728-731.
Metallo C.M., Gameiro P.A., Bell E.L., Mattaini K.R., Yang J., Hiller K., Jewell C.M., Johnson Z.R., Irvine D.J., Guarente L., Kelleher J.K., Vander Heiden M.G., Iliopoulos O., Stephanopoulos G. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012, 481:380-384.
Wise D.R., Ward P.S., Shay J.E., Cross J.R., Gruber J.J., Sachdeva U.M., Platt J.M., DeMatteo R.G., Simon M.C., Thompson C.B. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:19611-19616.
Leonardi R., Subramanian C., Jackowski S., Rock C.O. Cancer-associated isocitrate dehydrogenase mutations inactivate NADPH-dependent reductive carboxylation. J. Biol. Chem. 2012, 287:14615-14620.
Seltzer M.J., Bennett B.D., Joshi A.D., Gao P., Thomas A.G., Ferraris D.V., Tsukamoto T., Rojas C.J., Slusher B.S., Rabinowitz J.D., Dang C.V., Riggins G.J. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010, 70:8981-8987.
Wise D.R., Thompson C.B. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem. Sci. 2010, 35:427-433.
Ziskin J.L., Nishiyama A., Rubio M., Fukaya M., Bergles D.E. Vesicular release of glutamate from unmyelinated axons in white matter. Nat. Neurosci. 2007, 10:321-330.
Lecumberri E., Dupertuis Y.M., Miralbell R., Pichard C. Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy. Clin. Nutr. 2013, 32:894-903.
Ullmann U., Haller J., Decourt J.P., Girault N., Girault J., Richard-Caudron A.S., Pineau B., Weber P. A single ascending dose study of epigallocatechin gallate in healthy volunteers. J. Int. Med. Res. 2003, 31:88-101.
Jarzyna R., Lenarcik E., Bryla J. Chloroquine is a potent inhibitor of glutamate dehydrogenase in liver and kidney-cortex of rabbit. Pharmacol. Res. 1997, 35:79-84.
Maclean K.H., Dorsey F.C., Cleveland J.L., Kastan M.B. Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. J. Clin. Invest. 2008, 118:79-88.
Satoh M., Takemura Y., Hamada H., Sekido Y., Kubota S. EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy. Cancer Cell Int. 2013, 13:19.
Takeuchi S., Wada K., Toyooka T., Shinomiya N., Shimazaki H., Nakanishi K., Nagatani K., Otani N., Osada H., Uozumi Y., Matsuo H., Nawashiro H. Increased xCT expression correlates with tumor invasion and outcome in patients with glioblastomas. Neurosurgery 2013, 72:33-41. (discussion 41).
Sontheimer H., Bridges R.J. Sulfasalazine for brain cancer fits. Expert Opin. Invest. Drugs 2012, 21:575-578.
Rohle D., Popovici-Muller J., Palaskas N., Turcan S., Grommes C., Campos C., Tsoi J., Clark O., Oldrini B., Komisopoulou E., Kunii K., Pedraza A., Schalm S., Silverman L., Miller A., Wang F., Yang H., Chen Y., Kernytsky A., Rosenblum M.K., Liu W., Biller S.A., Su S.M., Brennan C.W., Chan T.A., Graeber T.G., Yen K.E., Mellinghoff I.K. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 2013, 340:626-630.
