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Isocitrate dehydrogenase mutations: new opportunities for translational research
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  • Journal title : BMB Reports
  • Volume 48, Issue 5,  2015, pp.266-270
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.5.021
 Title & Authors
Isocitrate dehydrogenase mutations: new opportunities for translational research
Keum, Young-Sam; Choi, Bu Young;
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 Abstract
Over the last decade, comprehensive genome-wide sequencing studies have enabled us to find out unexpected genetic alterations of metabolism in cancer. An example is the identification of arginine missense mutations of isocitrate dehydrogenases-1 and -2 (IDH1/2) in glioma, acute myeloid leukemia (AML), chondrosarcomas, and cholangiocarcinoma. These alterations are closely associated with the production of a new stereospecific metabolite, (R)-2-hydroxyglutarate (R-2HG). A large number of follow-up studies have been performed to address the molecular mechanisms of IDH1/2 mutations underlying how these events contribute to malignant transformation. In the meanwhile, the development of selective mutant IDH1/2 chemical inhibitors is being actively pursued in the scientific community and pharmaceutical industry. The present review article briefly discusses the important findings that highlight the molecular mechanisms of IDH1/2 mutations in cancer and provides a current status for development of selective mutant IDH1/2 chemical inhibitors. [BMB Reports 2015; 48(5): 266-270]
 Keywords
Cancer Metabolism;Isocitrate dehydrogenases (IDHs);Isocitrate (ICT);α-ketoglutarate (α-KG);(R)-2-hydroxyglutarate (R-2HG);
 Language
English
 Cited by
1.
Discovery of α-mangostin as a novel competitive inhibitor against mutant isocitrate dehydrogenase-1, Bioorganic & Medicinal Chemistry Letters, 2015, 25, 23, 5625  crossref(new windwow)
 References
1.
Warburg O (1956) On the origin of cancer cells. Science 123, 309-314 crossref(new window)

2.
Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Jr. and Kinzler KW (2013) Cancer genome landscapes. Science 339, 1546-1558 crossref(new window)

3.
Luo W and Semenza GL (2012) Emerging roles of PKM2 in cell metabolism and cancer progression. Trends Endocrinol Metab 23, 560-566 crossref(new window)

4.
Teicher BA, Linehan WM and Helman LJ (2012) Targeting cancer metabolism. Clin Cancer Res 18, 5537-5545 crossref(new window)

5.
Dang L, Jin S and Su SM (2010) IDH mutations in glioma and acute myeloid leukemia. Trends Mol Med 16, 387-397 crossref(new window)

6.
Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807-1812 crossref(new window)

7.
Sanson M, Marie Y, Paris S et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27, 4150-4154 crossref(new window)

8.
Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360, 765-773 crossref(new window)

9.
Bleeker FE, Lamba S, Leenstra S et al (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30, 7-11 crossref(new window)

10.
Xu X, Zhao J, Xu Z et al (2004) Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity. J Biol Chem 279, 33946-33957 crossref(new window)

11.
Oermann EK, Wu J, Guan KL and Xiong Y (2012) Alterations of metabolic genes and metabolites in cancer. Semin Cell Dev Biol 23, 370-380 crossref(new window)

12.
Watanabe T, Nobusawa S, Kleihues P and Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174, 1149-1153 crossref(new window)

13.
Losman JA and Kaelin WG Jr. (2013) What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev 27, 836-852 crossref(new window)

14.
Schwartzentruber J, Korshunov A, Liu XY et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482, 226-231 crossref(new window)

15.
Pollard PJ and Ratcliffe PJ (2009) Cancer. Puzzling patterns of predisposition. Science 324, 192-194 crossref(new window)

16.
Zhao S, Lin Y, Xu W et al (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science 324, 261-265 crossref(new window)

17.
Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462, 739-744 crossref(new window)

18.
Cairns RA and Mak TW (2013) Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities. Cancer Discov 3, 730-741 crossref(new window)

19.
Andronesi OC, Rapalino O, Gerstner E et al (2013) Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate. J Clin Invest 123, 3659-3663 crossref(new window)

20.
Sasaki M, Knobbe CB, Itsumi M et al (2012) D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function. Genes Dev 26, 2038-2049 crossref(new window)

21.
Sasaki M, Knobbe CB, Munger JC et al (2012) IDH1 (R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature 488, 656-659 crossref(new window)

22.
Kitamura T, Tange T, Terasawa T et al (1989) Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. J Cell Physiol 140, 323-334 crossref(new window)

23.
Losman JA, Looper RE, Koivunen P et al (2013) (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 339, 1621-1625 crossref(new window)

24.
Kranendijk M, Struys EA, Gibson KM et al (2010) Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. Hum Mutat 31, 279-283 crossref(new window)

25.
Struys EA, Salomons GS, Achouri Y et al (2005) Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Am J Hum Genet 76, 358-360 crossref(new window)

26.
Kranendijk M, Struys EA, van Schaftingen E et al (2010) IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science 330, 336 crossref(new window)

27.
Rohle D, Popovici-Muller J, Palaskas N et al (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340, 626-630 crossref(new window)

28.
Wang F, Travins J, DeLaBarre B et al (2013) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340, 622-626 crossref(new window)

29.
Popovici-Muller J, Saunders JO, Salituro FG et al (2012) Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo. ACS Med Chem Lett 3, 850-855 crossref(new window)

30.
Davis MI, Gross S, Shen M et al (2014) Biochemical, cellular, and biophysical characterization of a potent inhibitor of mutant isocitrate dehydrogenase IDH1. J Biol Chem 289, 13717-13725 crossref(new window)

31.
Liu Z, Yao Y, Kogiso M et al (2014) Inhibition of cancerassociated mutant isocitrate dehydrogenases: synthesis, structure-activity relationship, and selective antitumor activity. J Med Chem 57, 8307-8318 crossref(new window)

32.
Deng G, Shen J, Yin M et al (2015) Selective Inhibition of Mutant Isocitrate Dehydrogenase 1 (IDH1) via Disruption of a Metal Binding Network by an Allosteric Small Molecule. J Biol Chem 290, 762-774 crossref(new window)