Abstract
The metabolic pathways in cancer cells are reprogrammed such that they utilize nutrients quite differently than their normal, nonmalignant counterparts. It has been known for some time that the cancer phenotype results in alterations to glucose metabolism and, more recently, modifications to both glutamine and fatty acid metabolism have been noted. So prevalent is this altered metabolism in malignancy that many now consider it a hallmark of the cancer phenotype. As such, the metabolic discrepancies between cancer cells and normal cells provide a therapeutic window for the potential development of targeted anticancer agents. A number of pharmacological agents that either directly target the enzymes driving tumor glycolysis or the upstream mediators of the glycolytic pathway are currently under investigation with the hope of combining them with existing clinical protocols. Akin to the cytokines and chemokines produced by cancer cells, the intermediates and byproducts of altered tumor glycolysis, upon secretion from cancer cells, are also capable of modulating the phenotypes of normal cells located in the tumor microenvironment. Thus, glycolytic inhibitors may also rescue the effects that tumor derived metabolites have on surrounding cells.
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References
Bauer DE, Hatzivassiliou G, Zhao F et al (2005) Oncogene 24:6314–6322
Bayley JP, Devilee P (2012) The Warburg effect in 2012. Curr Opin Onco 24:62–67
Bonnett S, Archer SL, Allalunis-Turner J et al (2007) Cancer Cell 11:37–51
Bonucelli G, Tsirigos A, Whitaker-Menezes D et al (2010) Cell Cycle 9:3506–3513
Burger JA, Tsukada N, Burger M et al (2000) Blood 96:2655–2663
Cairns RA, Harris IS, Mak TW (2011) Nat Rev Cancer 11:85–95
Chang B, Chen Y, Zhao Y et al (2007) Science 318:444–447
Chou WC, Hou HA, Chen CY et al (2010) Blood 115:2749–2754
Clem B, Teland S, Clem A et al (2008) Mol Cancer Ther 7:110–120
Costa LT, Da Silva D, Guimaraes CR, Zancan P et al (2007) Biochem J 408:123–130
Dang CV (2012) Cell 149:22–35
Dang L, White DW, Gross S et al (2009) Nature 462:739–744
DeBerardinis RJ, Mancuso A, Daikhin E (2007) PNAS 104:19345–19350
Deprez J, Vertommen D, Alessi DR et al (1997) J Biol Chem 272:17269–17275
Dietl K, Renner K, Dettmer K (2010) J Immunol 184:1200–1209
Fantin VR, St-Pierre J, Leder P (2006) Cancer Cell 9:425–434
Figueroa ME, Abdel-Wahab O, Lu C et al (2010) Cancer Cell 18:553–567
Fischer K, Hoffman P, Voelkl S et al (2007) Blood 109:3812–3819
Floridi A, Paggi MG, Marcante ML et al (1981) J Natl Cancer Inst 66:497–499
Gottfried E, Kunz-Schughart LA, Ebner S et al (2006) Blood 107:2013–2021
Gottlob K, Majewski N, Kennedy S et al (2001) Genes Dev 15:1406–1418
Gross S, Cairns RA, Minden MD et al (2010) J Exp Med 207:339–344
Herman SE, Gordon AL, Wagner AJ et al (2010) Blood 116:2078–2088
Iwamoto S, Mihara K, Downing JR et al (2007) J Clin Invest 117:1049–1057
Jones RG, Thompson CB (2009) Genes Dev 23:537–548
Kioyi H, Naoe T, Nakano, Y et al (1999) Blood 93:3074–3080
Kohn AD, Summers SA, Birnbaum MJ et al (1996) J Biol Chem 271:31372–31378
Koivunen P, Lee S, Duncan CG (2012) Nature 483:484–488
Koukourakis MI, Giatromanolaki A, Harris AL et al (2006) Cancer Res 66:632–637
Krawczyk CM, Holowka T, Sun J et al (2009) Blood 115:4742–4749
Le A, Cooper CR, Gouw AM et al (2010) PNAS 107:2037–2042
Maher JC, Krishan A, Lampidis TJ (2004) Cancer Chemother Pharmacol 53:1745–1751
Manerba M, Vettraino, M, Fiume L et al (2012) Chem Med Chem 7:311–317
Mardis ER, Ding L, Dooling DJ et al (2010) N Engl J Med 361:1058–1066
Murray CM, Bundick ID, Cook, RI et al (2005) Nat Chem Biol 1:371–376
Nishio M, Endo T, Tsukada et al (2005) Blood 106:1012–1020
Rathmell JC, Farkash EA, Gao W, Thompson CB (2001) J Immunol 167:6869–6876
Reitman ZJ, Jon G, Karoly Ed et al (2011) PNAS 108:3270–3275
Scatena R, Bottoni P, Pontoglio A et al (2008) Expert Opin Invertis Drugs 17:1533–1545
Shim, H, Dolde, C, Lweis BC et al (1997) PNAS 94:6658–6663
Simioni C, Neri LM, Tabellini G et al (2012) Leukemia Epub ahead of publication 1–7
Sonveaux P, Vegran F, Schroeder T et al (2008) J Clin Invest 118:3930–3942
Tejada M, Gaal D, Hullan L et al (2006) Anticancer Red 26:3477–3483
Tennant DA, Duran R, Boulahbel H et al (2009) Carcinogenesis 30:1269–1280
Vivanco I, Sawyers CL (2002) Nat Rev Cancer 2:489–501
Walenta S, Wetterling M, Lehrke M et al (2000) Can Res 60:916–921
Walenta S, Schroeder T, Mueller-Klieser W (2004) Curr Med Chem 11:2195–2204
Warburg O (1956) Science 123:309–314
Warburg O, Wind F, Negelin E (1927) J Gen Physiol 8:519–530
Weisber E, Manley P, Mestan J et al (2006) Br J Cancer 94:1765–1769
Wise DR, DeBerardinis RJ, Mancuso A et al (2008) PNAS 105:18782–18787
Xu RH, Pelicano H, Zhang H, Giles FJ et al (2005) Leukemia 19:2153–2158
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Laister, R., Minden, M., Mak, T. (2015). Inhibition of Glycolysis as a Therapeutic Strategy in Acute Myeloid Leukemias. In: Andreeff, M. (eds) Targeted Therapy of Acute Myeloid Leukemia. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1393-0_38
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