IDH inhibitor
IDH inhibitors have shown good clinical response in AML patients. Based on phase 1/2 clinical trials, enasidenib and ivosidenib have been approved by the Food and Drug Administration (FDA) on 1 August 2017 and 20 July 2018 for the treatment of adult R/R AML with IDH2 and IDH1 mutations, respectively.
Allosteric inhibitors of mutant IDH1 or IDH2 induce terminal differentiation of the mutant leukemic blasts and provide durable clinical responses in approximately 40% of acute myeloid leukemia (AML) patients with the mutations. However, primary resistance and acquired resistance to the drugs are major clinical issues. To understand the molecular underpinnings of clinical resistance to IDH inhibitors (IDHi), Wang et al. performed multipronged genomic analyses (DNA sequencing, RNA sequencing, and cytosine methylation profiling) in longitudinally collected specimens from 60 IDH1- or IDH2-mutant AML patients treated with the inhibitors. The analysis reveals that leukemia stemness is a major driver of primary resistance to IDHi, whereas selection of mutations in RUNX1/CEBPA or RAS-RTK pathway genes is the main driver of acquired resistance to IDHi, along with BCOR, homologous IDH gene, and TET2. These data suggest that targeting stemness and certain high-risk co-occurring mutations may overcome resistance to IDHi in AML. 1)
2: Förster A, Brand F, Banan R, Hüneburg R, Weber CAM, Ewert W, Kronenberg J, Previti C, Elyan N, Beyer U, Martens H, Hong B, Bräsen JH, Erbersdobler A, Krauss JK, Stangel M, Samii A, Wolf S, Preller M, Aretz S, Wiese B, Hartmann C, Weber RG. Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin. Acta Neuropathol. 2021 Apr 30. doi: 10.1007/s00401-021-02307-1. Epub ahead of print. PMID: 33929593.
3: Schittenhelm J, Ziegler L, Sperveslage J, Mittelbronn M, Capper D, Burghardt I, Poso A, Biskup S, Skardelly M, Tabatabai G. FGFR3 overexpression is a useful detection tool for FGFR3 fusions and sequence variations in glioma. Neurooncol Pract. 2020 Nov 20;8(2):209-221. doi: 10.1093/nop/npaa075. PMID: 33898054; PMCID: PMC8049444.
4: Georgescu MM, Islam MZ, Li Y, Traylor J, Nanda A. Novel targetable FGFR2 and FGFR3 alterations in glioblastoma associate with aggressive phenotype and distinct gene expression programs. Acta Neuropathol Commun. 2021 Apr 14;9(1):69. doi: 10.1186/s40478-021-01170-1. PMID: 33853673; PMCID: PMC8048363.
5: Mair MJ, Kiesel B, Feldmann K, Widhalm G, Dieckmann K, Wöhrer A, Müllauer L, Preusser M, Berghoff AS. LAG-3 expression in the inflammatory microenvironment of glioma. J Neurooncol. 2021 May;152(3):533-539. doi: 10.1007/s11060-021-03721-x. Epub 2021 Mar 2. PMID: 33651248; PMCID: PMC8084780.
6: Ge J, Li C, Xue F, Qi S, Gao Z, Yu C, Zhang J. Apatinib Plus Temozolomide: An Effective Salvage Treatment for Glioblastoma recurrence. Front Oncol. 2021 Feb 4;10:601175. doi: 10.3389/fonc.2020.601175. PMID: 33634023; PMCID: PMC7901881.
7: Huang GD, Chen FF, Ma GX, Li WP, Zheng YY, Meng XB, Li ZY, Chen L. Cassane diterpenoid derivative induces apoptosis in IDH1 mutant glioma cells through the inhibition of glutaminase in vitro and in vivo. Phytomedicine. 2021 Feb;82:153434. doi: 10.1016/j.phymed.2020.153434. Epub 2020 Dec 11. PMID: 33529962.
8: Nimbalkar VP, Kruthika BS, Sravya P, Rao S, Sugur HS, Verma BK, Chickabasaviah YT, Arivazhagan A, Kondaiah P, Santosh V. Differential gene expression in peritumoral brain zone of glioblastoma: role of SERPINA3 in promoting invasion, stemness and radioresistance of glioma cells and association with poor patient prognosis and recurrence. J Neurooncol. 2021 Mar;152(1):55-65. doi: 10.1007/s11060-020-03685-4. Epub 2021 Jan 3. PMID: 33389566.
9: Park JW, Kang J, Lim KY, Kim H, Kim SI, Won JK, Park CK, Park SH. The prognostic significance of p16 expression pattern in diffuse gliomas. J Pathol Transl Med. 2021 Mar;55(2):102-111. doi: 10.4132/jptm.2020.10.22. Epub 2020 Dec 23. PMID: 33348944; PMCID: PMC7987518.
10: Kadiyala P, Carney SV, Gauss JC, Garcia-Fabiani MB, Haase S, Alghamri MS, Núñez FJ, Liu Y, Yu M, Taher A, Nunez FM, Li D, Edwards MB, Kleer CG, Appelman H, Sun Y, Zhao L, Moon JJ, Schwendeman A, Lowenstein PR, Castro MG. Inhibition of 2-hydroxyglutarate elicits metabolic reprogramming and mutant IDH1 glioma immunity in mice. J Clin Invest. 2021 Feb 15;131(4):e139542. doi: 10.1172/JCI139542. PMID: 33332283; PMCID: PMC7880418.
11: Dono A, Vu J, Anapolsky M, Hines G, Takayasu T, Yan Y, Tandon N, Zhu JJ, Bhattacharjee MB, Esquenazi Y, Ballester LY. Additional genetic alterations in BRAF-mutant gliomas correlate with histologic diagnoses. J Neurooncol. 2020 Sep;149(3):463-472. doi: 10.1007/s11060-020-03634-1. Epub 2020 Oct 3. PMID: 33009979; PMCID: PMC7642042.
12: Wang Y, Liang D, Chen J, Chen H, Fan R, Gao Y, Gao Y, Tao R, Zhang H. Targeted Therapy with Anlotinib for a Patient with an Oncogenic FGFR3-TACC3 Fusion and Glioblastoma recurrence. Oncologist. 2021 Mar;26(3):173-177. doi: 10.1002/onco.13530. Epub 2020 Oct 3. PMID: 32949176; PMCID: PMC7930428.
13: Caccese M, Ius T, Simonelli M, Fassan M, Cesselli D, Dipasquale A, Cavallin F, Padovan M, Salvalaggio A, Gardiman MP, Skrap M, Zagonel V, Lombardi G. Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study. Int J Mol Sci. 2020 Sep 14;21(18):6716. doi: 10.3390/ijms21186716. PMID: 32937743; PMCID: PMC7555820.
14: Zhang Y, Xie Y, He L, Tang J, He Q, Cao Q, Cui L, Guo W, Hua K, Dimberg A, Wang L, Zhang L. 1p/19q co-deletion status is associated with distinct tumor- associated macrophage infiltration in IDH mutated lower-grade gliomas. Cell Oncol (Dordr). 2021 Feb;44(1):193-204. doi: 10.1007/s13402-020-00561-1. Epub 2020 Sep 11. PMID: 32915415.
15: Waitkus MS, Yan H. Targeting Isocitrate Dehydrogenase Mutations in Cancer: Emerging Evidence and Diverging Strategies. Clin Cancer Res. 2021 Jan 15;27(2):383-388. doi: 10.1158/1078-0432.CCR-20-1827. Epub 2020 Sep 3. PMID: 32883741.
16: Park JW, Sahm F, Steffl B, Arrillaga-Romany I, Cahill D, Monje M, Herold- Mende C, Wick W, Turcan Ş. TERT and DNMT1 expression predict sensitivity to decitabine in gliomas. Neuro Oncol. 2021 Jan 30;23(1):76-87. doi: 10.1093/neuonc/noaa207. PMID: 32882013; PMCID: PMC7850113.
17: Zhang H, Zhou Y, Cheng Q, Dai Z, Wang Z, Liu F, Fan F, Cui B, Cao H. PDIA3 correlates with clinical malignant features and immune signature in human gliomas. Aging (Albany NY). 2020 Aug 29;12(15):15392-15413. doi: 10.18632/aging.103601. PMID: 32687065; PMCID: PMC7467394.
18: Oh S, Yeom J, Cho HJ, Kim JH, Yoon SJ, Kim H, Sa JK, Ju S, Lee H, Oh MJ, Lee W, Kwon Y, Li H, Choi S, Han JH, Chang JH, Choi E, Kim J, Her NG, Kim SH, Kang SG, Paek E, Nam DH, Lee C, Kim HS. Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities. Nat Commun. 2020 Jul 3;11(1):3288. doi: 10.1038/s41467-020-17139-y. PMID: 32620753; PMCID: PMC7335111.
19: Roth P, Hottinger AF, Hundsberger T, Läubli H, Schucht P, Reinert M, Mamot C, Roelcke U, Pesce G, Hofer S, Weller M. A contemporary perspective on the diagnosis and treatment of diffuse gliomas in adults. Swiss Med Wkly. 2020 Jun 18;150:w20256. doi: 10.4414/smw.2020.20256. PMID: 32557428.
20: Lu VM, O'Connor KP, Shah AH, Eichberg DG, Luther EM, Komotar RJ, Ivan ME. The prognostic significance of CDKN2A homozygous deletion in IDH-mutant lower- grade glioma and glioblastoma: a systematic review of the contemporary literature. J Neurooncol. 2020 Jun;148(2):221-229. doi: 10.1007/s11060-020-03528-2. Epub 2020 May 8. PMID: 32385699.
21: Mohme M, Maire CL, Schliffke S, Joosse SA, Alawi M, Matschke J, Schüller U, Dierlamm J, Martens T, Pantel K, Riethdorf S, Lamszus K, Westphal M. Molecular profiling of an osseous metastases in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape. Acta Neuropathol Commun. 2020 Mar 9;8(1):28. doi: 10.1186/s40478-020-00906-9. PMID: 32151286; PMCID: PMC7063778.
22: Umphlett M, Shea S, Tome-Garcia J, Zhang Y, Hormigo A, Fowkes M, Tsankova NM, Yong RL. Widely metastatic glioblastoma with BRCA1 and ARID1A mutations: a case report. BMC Cancer. 2020 Jan 20;20(1):47. doi: 10.1186/s12885-020-6540-1. PMID: 31959133; PMCID: PMC6971940.
23: Li GZ, Zhang KN, Wang Z, Hu HM, Wang ZL, Huang RY, Jiang HY, Zhai Y, Feng YM, Chang YH, Li RP, Wu F, Zeng F, Jiang T, Zhang W. Siglecs, Novel Immunotherapy Targets, Potentially Enhance The Effectiveness of Existing Immune Checkpoint Inhibitors in Glioma Immunotherapy. Onco Targets Ther. 2019 Nov 27;12:10263-10273. doi: 10.2147/OTT.S223406. PMID: 31819511; PMCID: PMC6885574.
24: Karpel-Massler G, Nguyen TTT, Shang E, Siegelin MD. Novel IDH1-Targeted Glioma Therapies. CNS Drugs. 2019 Dec;33(12):1155-1166. doi: 10.1007/s40263-019-00684-6. PMID: 31768950; PMCID: PMC7027940.
25: Zeiner PS, Kinzig M, Divé I, Maurer GD, Filipski K, Harter PN, Senft C, Bähr O, Hattingen E, Steinbach JP, Sörgel F, Voss M, Steidl E, Ronellenfitsch MW. Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients. J Clin Med. 2019 Nov 21;8(12):2031. doi: 10.3390/jcm8122031. PMID: 31766326; PMCID: PMC6947028.
26: Reinhardt A, Stichel D, Schrimpf D, Koelsche C, Wefers AK, Ebrahimi A, Sievers P, Huang K, Casalini MB, Fernández-Klett F, Suwala A, Weller M, Gramatzki D, Felsberg J, Reifenberger G, Becker A, Hans VH, Prinz M, Staszewski O, Acker T, Dohmen H, Hartmann C, Paulus W, Heß K, Brokinkel B, Schittenhelm J, Buslei R, Deckert M, Mawrin C, Hewer E, Pohl U, Jaunmuktane Z, Brandner S, Unterberg A, Hänggi D, Platten M, Pfister SM, Wick W, Herold-Mende C, Korshunov A, Reuss DE, Sahm F, Jones DTW, Capper D, von Deimling A. Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities. Acta Neuropathol Commun. 2019 Oct 28;7(1):163. doi: 10.1186/s40478-019-0801-8. PMID: 31661039; PMCID: PMC6816155.
27: Wu Y, Li Z, Zhang L, Liu G. Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling. Med Sci Monit. 2019 Oct 2;25:7383-7390. doi: 10.12659/MSM.919319. PMID: 31575848; PMCID: PMC6790099.
28: Bhavya B, Anand CR, Madhusoodanan UK, Rajalakshmi P, Krishnakumar K, Easwer HV, Deepti AN, Gopala S. To be Wild or Mutant: Role of Isocitrate Dehydrogenase 1 (IDH1) and 2-Hydroxy Glutarate (2-HG) in Gliomagenesis and Treatment Outcome in Glioma. Cell Mol Neurobiol. 2020 Jan;40(1):53-63. doi: 10.1007/s10571-019-00730-3. Epub 2019 Sep 4. PMID: 31485826.
29: Wirsching HG, Arora S, Zhang H, Szulzewsky F, Cimino PJ, Quéva C, Houghton AM, Glorioso JC, Weller M, Holland EC. Cooperation of oncolytic virotherapy with VEGF-neutralizing antibody treatment in IDH wildtype glioblastoma depends on MMP9. Neuro Oncol. 2019 Dec 17;21(12):1607-1609. doi: 10.1093/neuonc/noz145. PMID: 31412117; PMCID: PMC6917394.
30: Wirsching HG, Zhang H, Szulzewsky F, Arora S, Grandi P, Cimino PJ, Amankulor N, Campbell JS, McFerrin L, Pattwell SS, Ene C, Hicks A, Ball M, Yan J, Zhang J, Kumasaka D, Pierce RH, Weller M, Finer M, Quéva C, Glorioso JC, Houghton AM, Holland EC. Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte- depleted glioblastoma. JCI Insight. 2019 Jul 11;4(13):e128217. doi: 10.1172/jci.insight.128217. PMID: 31292299; PMCID: PMC6629248.
31: Zhang Y, Lv W, Li Q, Wang Q, Ru Y, Xiong X, Yan F, Pan T, Lin W, Li X. IDH2 compensates for IDH1 mutation to maintain cell survival under hypoxic conditions in IDH1‑mutant tumor cells. Mol Med Rep. 2019 Aug;20(2):1893-1900. doi: 10.3892/mmr.2019.10418. Epub 2019 Jun 24. PMID: 31257503.
32: Golub D, Iyengar N, Dogra S, Wong T, Bready D, Tang K, Modrek AS, Placantonakis DG. Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics. Front Oncol. 2019 May 17;9:417. doi: 10.3389/fonc.2019.00417. PMID: 31165048; PMCID: PMC6534082.
33: Kaminska B, Czapski B, Guzik R, Król SK, Gielniewski B. Consequences of <i>IDH1/2</i> Mutations in Gliomas and an Assessment of Inhibitors Targeting Mutated IDH Proteins. Molecules. 2019 Mar 9;24(5):968. doi: 10.3390/molecules24050968. PMID: 30857299; PMCID: PMC6429355.
34: Cardona AF, Rojas L, Wills B, Ruiz-Patiño A, Abril L, Hakim F, Jiménez E, Useche N, Bermúdez S, Mejía JA, Ramón JF, Carranza H, Vargas C, Otero J, Archila P, Rodríguez J, Rodríguez J, Behaine J, González D, Jacobo J, Cifuentes H, Feo O, Penagos P, Pineda D, Ricaurte L, Pino LE, Vargas C, Marquez JC, Mantilla MI, Ortiz LD, Balaña C, Rosell R, Zatarain-Barrón ZL, Arrieta O. A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma. Clin Transl Oncol. 2019 Oct;21(10):1364-1373. doi: 10.1007/s12094-019-02066-2. Epub 2019 Feb 23. PMID: 30798512.
35: Wang ZL, Li GZ, Wang QW, Bao ZS, Wang Z, Zhang CB, Jiang T. PD-L2 expression is correlated with the molecular and clinical features of glioma, and acts as an unfavorable prognostic factor. Oncoimmunology. 2018 Nov 20;8(2):e1541535. doi: 10.1080/2162402X.2018.1541535. PMID: 30713802; PMCID: PMC6343813.
36: Guan X, Luo L, Begum G, Kohanbash G, Song Q, Rao A, Amankulor N, Sun B, Sun D, Jia W. Elevated Na/H exchanger 1 (SLC9A1) emerges as a marker for tumorigenesis and prognosis in gliomas. J Exp Clin Cancer Res. 2018 Oct 17;37(1):255. doi: 10.1186/s13046-018-0923-z. PMID: 30333031; PMCID: PMC6192309.
37: Schwartz C, Romagna A, Machegger L, Weiss L, Huemer F, Fastner G, Kleindienst W, Weis S, Greil R, Winkler PA. Extensive Leptomeningeal Intracranial and Spinal Metastases in a Patient with a Supratentorial Glioblastoma Multiforme, IDH-Wildtype. World Neurosurg. 2018 Dec;120:442-447. doi: 10.1016/j.wneu.2018.09.082. Epub 2018 Sep 22. PMID: 30253992.
38: McBrayer SK, Mayers JR, DiNatale GJ, Shi DD, Khanal J, Chakraborty AA, Sarosiek KA, Briggs KJ, Robbins AK, Sewastianik T, Shareef SJ, Olenchock BA, Parker SJ, Tateishi K, Spinelli JB, Islam M, Haigis MC, Looper RE, Ligon KL, Bernstein BE, Carrasco RD, Cahill DP, Asara JM, Metallo CM, Yennawar NH, Vander Heiden MG, Kaelin WG Jr. Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma. Cell. 2018 Sep 20;175(1):101-116.e25. doi: 10.1016/j.cell.2018.08.038. Epub 2018 Sep 13. PMID: 30220459; PMCID: PMC6219629.
39: Yao Y, Luo F, Tang C, Chen D, Qin Z, Hua W, Xu M, Zhong P, Yu S, Chen D, Ding X, Zhang Y, Zheng X, Yang J, Qian J, Deng Y, Hoon DSB, Hu J, Chu Y, Zhou L. Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial. Cancer Immunol Immunother. 2018 Nov;67(11):1777-1788. doi: 10.1007/s00262-018-2232-y. Epub 2018 Aug 22. PMID: 30159779.
40: Shankar GM, Kirtane AR, Miller JJ, Mazdiyasni H, Rogner J, Tai T, Williams EA, Higuchi F, Juratli TA, Tateishi K, Koerner MVA, Tummala SS, Fink AL, Penson T, Schmidt SP, Wojtkiewicz GR, Baig A, Francis JM, Rinne ML, Batten JM, Batchelor TT, Brastianos PK, Curry WT Jr, Barker FG 2nd, Jordan JT, Iafrate AJ, Chi AS, Lennerz JK, Meyerson M, Langer R, Wakimoto H, Traverso G, Cahill DP. Genotype-targeted local therapy of glioma. Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8388-E8394. doi: 10.1073/pnas.1805751115. Epub 2018 Aug 6. PMID: 30082399; PMCID: PMC6130372.
41: Wang Z, Wang Z, Zhang C, Liu X, Li G, Liu S, Sun L, Liang J, Hu H, Liu Y, Zhang W, Jiang T. Genetic and clinical characterization of B7-H3 (CD276) expression and epigenetic regulation in diffuse brain glioma. Cancer Sci. 2018 Sep;109(9):2697-2705. doi: 10.1111/cas.13744. Epub 2018 Aug 29. PMID: 30027617; PMCID: PMC6125452.
42: Gao Y, de Wit M, Struys EA, van der Linde HCZ, Salomons GS, Lamfers MLM, Willemsen R, Sillevis Smitt PAE, French PJ. IDH1-mutated transgenic zebrafish lines: An in-vivo model for drug screening and functional analysis. PLoS One. 2018 Jun 28;13(6):e0199737. doi: 10.1371/journal.pone.0199737. PMID: 29953513; PMCID: PMC6023169.
43: Le BH, Close RA. Imaging and Histopathologic Nuances of Epithelioid Glioblastoma. Case Rep Surg. 2018 May 22;2018:1285729. doi: 10.1155/2018/1285729. PMID: 29951334; PMCID: PMC5987230.
44: Deng MY, Sill M, Chiang J, Schittenhelm J, Ebinger M, Schuhmann MU, Monoranu CM, Milde T, Wittmann A, Hartmann C, Sommer C, Paulus W, Gärtner J, Brück W, Rüdiger T, Leipold A, Jaunmuktane Z, Brandner S, Giangaspero F, Nozza P, Mora J, Morales la Madrid A, Cruz Martinez O, Hansford JR, Pietsch T, Tietze A, Hernáiz- Driever P, Stoler I, Capper D, Korshunov A, Ellison DW, von Deimling A, Pfister SM, Sahm F, Jones DTW. Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features. Acta Neuropathol. 2018 Aug;136(2):239-253. doi: 10.1007/s00401-018-1865-4. Epub 2018 May 15. PMID: 29766299.
45: Wang PF, Cai HQ, Zhang CB, Li YM, Liu X, Wan JH, Jiang T, Li SW, Yan CX. Molecular and clinical characterization of PTPN2 expression from RNA-seq data of 996 brain gliomas. J Neuroinflammation. 2018 May 15;15(1):145. doi: 10.1186/s12974-018-1187-4. PMID: 29764444; PMCID: PMC5953404.
46: Shirahata M, Ono T, Stichel D, Schrimpf D, Reuss DE, Sahm F, Koelsche C, Wefers A, Reinhardt A, Huang K, Sievers P, Shimizu H, Nanjo H, Kobayashi Y, Miyake Y, Suzuki T, Adachi JI, Mishima K, Sasaki A, Nishikawa R, Bewerunge- Hudler M, Ryzhova M, Absalyamova O, Golanov A, Sinn P, Platten M, Jungk C, Winkler F, Wick A, Hänggi D, Unterberg A, Pfister SM, Jones DTW, van den Bent M, Hegi M, French P, Baumert BG, Stupp R, Gorlia T, Weller M, Capper D, Korshunov A, Herold-Mende C, Wick W, Louis DN, von Deimling A. Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. Acta Neuropathol. 2018 Jul;136(1):153-166. doi: 10.1007/s00401-018-1849-4. Epub 2018 Apr 23. PMID: 29687258.
47: Mu L, Long Y, Yang C, Jin L, Tao H, Ge H, Chang YE, Karachi A, Kubilis PS, De Leon G, Qi J, Sayour EJ, Mitchell DA, Lin Z, Huang J. The IDH1 Mutation- Induced Oncometabolite, 2-Hydroxyglutarate, May Affect DNA Methylation and Expression of PD-L1 in Gliomas. Front Mol Neurosci. 2018 Mar 28;11:82. doi: 10.3389/fnmol.2018.00082. PMID: 29643764; PMCID: PMC5882817.
48: Ohba S, Hirose Y. Association between mutant IDHs and tumorigenesis in gliomas. Med Mol Morphol. 2018 Dec;51(4):194-198. doi: 10.1007/s00795-018-0189-8. Epub 2018 Apr 9. PMID: 29633022.
49: Reinhardt A, Stichel D, Schrimpf D, Sahm F, Korshunov A, Reuss DE, Koelsche C, Huang K, Wefers AK, Hovestadt V, Sill M, Gramatzki D, Felsberg J, Reifenberger G, Koch A, Thomale UW, Becker A, Hans VH, Prinz M, Staszewski O, Acker T, Dohmen H, Hartmann C, Mueller W, Tuffaha MSA, Paulus W, Heß K, Brokinkel B, Schittenhelm J, Monoranu CM, Kessler AF, Loehr M, Buslei R, Deckert M, Mawrin C, Kohlhof P, Hewer E, Olar A, Rodriguez FJ, Giannini C, NageswaraRao AA, Tabori U, Nunes NM, Weller M, Pohl U, Jaunmuktane Z, Brandner S, Unterberg A, Hänggi D, Platten M, Pfister SM, Wick W, Herold-Mende C, Jones DTW, von Deimling A, Capper D. Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations. Acta Neuropathol. 2018 Aug;136(2):273-291. doi: 10.1007/s00401-018-1837-8. Epub 2018 Mar 21. PMID: 29564591.
50: Li T, Cox CD, Ozer BH, Nguyen NT, Nguyen HN, Lai TJ, Li S, Liu F, Kornblum HI, Liau LM, Nghiemphu PL, Cloughesy TF, Lai A. D-2-Hydroxyglutarate Is Necessary and Sufficient for Isocitrate Dehydrogenase 1 Mutant-Induced <i>MIR148A</i> Promoter Methylation. Mol Cancer Res. 2018 Jun;16(6):947-960. doi: 10.1158/1541-7786.MCR-17-0367. Epub 2018 Mar 15. PMID: 29545476; PMCID: PMC5984679.
51: Hersh DS, Peng S, Dancy JG, Galisteo R, Eschbacher JM, Castellani RJ, Heath JE, Legesse T, Kim AJ, Woodworth GF, Tran NL, Winkles JA. Differential expression of the TWEAK receptor Fn14 in IDH1 wild-type and mutant gliomas. J Neurooncol. 2018 Jun;138(2):241-250. doi: 10.1007/s11060-018-2799-3. Epub 2018 Feb 16. PMID: 29453678; PMCID: PMC6047063.
52: Neal A, Kwan P, O'Brien TJ, Buckland ME, Gonzales M, Morokoff A. IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy. Epilepsy Behav. 2018 Jan;78:30-36. doi: 10.1016/j.yebeh.2017.10.027. Epub 2017 Dec 22. PMID: 29172136.
53: Nakajima N, Nobusawa S, Nakata S, Nakada M, Yamazaki T, Matsumura N, Harada K, Matsuda H, Funata N, Nagai S, Nakamura H, Sasaki A, Akimoto J, Hirato J, Yokoo H. BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions are frequent in epithelioid glioblastomas: a histological and molecular analysis focusing on intratumoral heterogeneity. Brain Pathol. 2018 Sep;28(5):663-673. doi: 10.1111/bpa.12572. Epub 2017 Dec 5. PMID: 29105198.
54: Brandner S, Jaunmuktane Z. Neurological update: gliomas and other primary brain tumours in adults. J Neurol. 2018 Mar;265(3):717-727. doi: 10.1007/s00415-017-8652-3. Epub 2017 Nov 2. PMID: 29098416; PMCID: PMC5834564.
55: Waitkus MS, Pirozzi CJ, Moure CJ, Diplas BH, Hansen LJ, Carpenter AB, Yang R, Wang Z, Ingram BO, Karoly ED, Mohney RP, Spasojevic I, McLendon RE, Friedman HS, He Y, Bigner DD, Yan H. Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities. Cancer Res. 2018 Jan 1;78(1):36-50. doi: 10.1158/0008-5472.CAN-17-1352. Epub 2017 Nov 2. PMID: 29097607; PMCID: PMC5754242.
56: Modrek AS, Golub D, Khan T, Bready D, Prado J, Bowman C, Deng J, Zhang G, Rocha PP, Raviram R, Lazaris C, Stafford JM, LeRoy G, Kader M, Dhaliwal J, Bayin NS, Frenster JD, Serrano J, Chiriboga L, Baitalmal R, Nanjangud G, Chi AS, Golfinos JG, Wang J, Karajannis MA, Bonneau RA, Reinberg D, Tsirigos A, Zagzag D, Snuderl M, Skok JA, Neubert TA, Placantonakis DG. Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2. Cell Rep. 2017 Oct 31;21(5):1267-1280. doi: 10.1016/j.celrep.2017.10.009. PMID: 29091765; PMCID: PMC5687844.
57: Karpel-Massler G, Ishida CT, Bianchetti E, Zhang Y, Shu C, Tsujiuchi T, Banu MA, Garcia F, Roth KA, Bruce JN, Canoll P, Siegelin MD. Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL. Nat Commun. 2017 Oct 20;8(1):1067. doi: 10.1038/s41467-017-00984-9. PMID: 29057925; PMCID: PMC5651864.
58: Nam JY, de Groot JF. Treatment of Glioblastoma. J Oncol Pract. 2017 Oct;13(10):629-638. doi: 10.1200/JOP.2017.025536. PMID: 29020535.
59: Berghoff AS, Kiesel B, Widhalm G, Wilhelm D, Rajky O, Kurscheid S, Kresl P, Wöhrer A, Marosi C, Hegi ME, Preusser M. Correlation of immune phenotype with IDH mutation in diffuse glioma. Neuro Oncol. 2017 Oct 19;19(11):1460-1468. doi: 10.1093/neuonc/nox054. PMID: 28531337; PMCID: PMC5737620.
60: Jin C, Li M, Ouyang Y, Tan Z, Jiang Y. MiR-424 functions as a tumor suppressor in glioma cells and is down-regulated by DNA methylation. J Neurooncol. 2017 Jun;133(2):247-255. doi: 10.1007/s11060-017-2438-4. Epub 2017 May 15. PMID: 28508328.
61: Granberg KJ, Annala M, Lehtinen B, Kesseli J, Haapasalo J, Ruusuvuori P, Yli-Harja O, Visakorpi T, Haapasalo H, Nykter M, Zhang W. Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas. Neuro Oncol. 2017 Sep 1;19(9):1206-1216. doi: 10.1093/neuonc/nox028. PMID: 28379477; PMCID: PMC5570261.
62: Ohka F, Yamamichi A, Kurimoto M, Motomura K, Tanahashi K, Suzuki H, Aoki K, Deguchi S, Chalise L, Hirano M, Kato A, Nishimura Y, Hara M, Kato Y, Wakabayashi T, Natsume A. A novel all-in-one intraoperative genotyping system for IDH1-mutant glioma. Brain Tumor Pathol. 2017 Apr;34(2):91-97. doi: 10.1007/s10014-017-0281-0. Epub 2017 Mar 28. PMID: 28353033.
63: Szopa W, Burley TA, Kramer-Marek G, Kaspera W. Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives. Biomed Res Int. 2017;2017:8013575. doi: 10.1155/2017/8013575. Epub 2017 Feb 20. PMID: 28316990; PMCID: PMC5337853.
64: Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Sci Transl Med. 2017 Feb 1;9(375):eaal2463. doi: 10.1126/scitranslmed.aal2463. PMID: 28148839; PMCID: PMC5435119.
65: Pusch S, Krausert S, Fischer V, Balss J, Ott M, Schrimpf D, Capper D, Sahm F, Eisel J, Beck AC, Jugold M, Eichwald V, Kaulfuss S, Panknin O, Rehwinkel H, Zimmermann K, Hillig RC, Guenther J, Toschi L, Neuhaus R, Haegebart A, Hess- Stumpp H, Bauser M, Wick W, Unterberg A, Herold-Mende C, Platten M, von Deimling A. Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo. Acta Neuropathol. 2017 Apr;133(4):629-644. doi: 10.1007/s00401-017-1677-y. Epub 2017 Jan 25. PMID: 28124097.
66: Reich TR, Switzeny OJ, Renovanz M, Sommer C, Kaina B, Christmann M, Tomicic MT. Epigenetic silencing of XAF1 in high-grade gliomas is associated with IDH1 status and improved clinical outcome. Oncotarget. 2017 Feb 28;8(9):15071-15084. doi: 10.18632/oncotarget.14748. PMID: 28122345; PMCID: PMC5362468.
67: Wang Z, Zhang C, Liu X, Wang Z, Sun L, Li G, Liang J, Hu H, Liu Y, Zhang W, Jiang T. Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma. Oncoimmunology. 2016 Jun 16;5(11):e1196310. doi: 10.1080/2162402X.2016.1196310. PMID: 27999734; PMCID: PMC5139638.
68: Schliesser MG, Claus R, Hielscher T, Grimm C, Weichenhan D, Blaes J, Wiestler B, Hau P, Schramm J, Sahm F, Weiß EK, Weiler M, Baer C, Schmidt-Graf F, Schackert G, Westphal M, Hertenstein A, Roth P, Galldiks N, Hartmann C, Pietsch T, Felsberg J, Reifenberger G, Sabel MC, Winkler F, von Deimling A, Meisner C, Vajkoczy P, Platten M, Weller M, Plass C, Wick W. Prognostic relevance of miRNA-155 methylation in anaplastic glioma. Oncotarget. 2016 Dec 13;7(50):82028-82045. doi: 10.18632/oncotarget.13452. PMID: 27880937; PMCID: PMC5347671.
69: Ogasawara S, Fujii Y, Kaneko MK, Oki H, Sabit H, Nakada M, Suzuki H, Ichimura K, Komori T, Kato Y. Establishment of Anti-Human ATRX Monoclonal Antibody AMab-6. Monoclon Antib Immunodiagn Immunother. 2016 Oct;35(5):254-258. doi: 10.1089/mab.2016.0037. PMID: 27788029; PMCID: PMC5160166.
70: Miller JJ, Curry WT, Cahill DP, Dietrich J. Perspectives on investigational drugs and immunotherapies for glioblastoma. Expert Opin Investig Drugs. 2016 Sep;25(9):1007-9. doi: 10.1080/13543784.2016.1213242. PMID: 27415034; PMCID: PMC5018991.
71: Chen R, Cohen AL, Colman H. Targeted Therapeutics in Patients With High- Grade Gliomas: Past, Present, and Future. Curr Treat Options Oncol. 2016 Aug;17(8):42. doi: 10.1007/s11864-016-0418-0. PMID: 27334978.
72: Lohkamp LN, Schinz M, Gehlhaar C, Guse K, Thomale UW, Vajkoczy P, Heppner FL, Koch A. MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma. PLoS One. 2016 Jun 2;11(6):e0156422. doi: 10.1371/journal.pone.0156422. PMID: 27253461; PMCID: PMC4890800.
73: Montano N, D'Alessandris QG, Izzo A, Fernandez E, Pallini R. Biomarkers for glioblastoma multiforme: status quo. J Clin Transl Res. 2016 Mar 27;2(1):3-10. PMID: 30873456; PMCID: PMC6410643.
74: Wang P, Wu J, Ma S, Zhang L, Yao J, Hoadley KA, Wilkerson MD, Perou CM, Guan KL, Ye D, Xiong Y. Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents. Cell Rep. 2015 Dec 22;13(11):2353-2361. doi: 10.1016/j.celrep.2015.11.029. Epub 2015 Dec 10. PMID: 26686626; PMCID: PMC4694633.
75: Kanamori M, Suzuki H, Takei H, Sonoda Y, Uenohara H, Tominaga T. Malignant transformation of diffuse astrocytoma to glioblastoma associated with newly developed BRAF V600E mutation. Brain Tumor Pathol. 2016 Jan;33(1):50-6. doi: 10.1007/s10014-015-0231-7. Epub 2015 Sep 24. PMID: 26404554.
76: Molenaar RJ, Botman D, Smits MA, Hira VV, van Lith SA, Stap J, Henneman P, Khurshed M, Lenting K, Mul AN, Dimitrakopoulou D, van Drunen CM, Hoebe RA, Radivoyevitch T, Wilmink JW, Maciejewski JP, Vandertop WP, Leenders WP, Bleeker FE, van Noorden CJ. Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198. Cancer Res. 2015 Nov 15;75(22):4790-802. doi: 10.1158/0008-5472.CAN-14-3603. Epub 2015 Sep 11. PMID: 26363012.
77: Birner P, Tchorbanov A, Natchev S, Tuettenberg J, Guentchev M. The chemokine receptor CXCR7 influences prognosis in human glioma in an IDH1-dependent manner. J Clin Pathol. 2015 Oct;68(10):830-4. doi: 10.1136/jclinpath-2015-202886. Epub 2015 Jun 24. PMID: 26109200.
78: Reis GF, Pekmezci M, Hansen HM, Rice T, Marshall RE, Molinaro AM, Phillips JJ, Vogel H, Wiencke JK, Wrensch MR, Walsh KM, Perry A. CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas. J Neuropathol Exp Neurol. 2015 May;74(5):442-52. doi: 10.1097/NEN.0000000000000188. PMID: 25853694; PMCID: PMC4397174.
79: Di Stefano AL, Fucci A, Frattini V, Labussiere M, Mokhtari K, Zoppoli P, Marie Y, Bruno A, Boisselier B, Giry M, Savatovsky J, Touat M, Belaid H, Kamoun A, Idbaih A, Houillier C, Luo FR, Soria JC, Tabernero J, Eoli M, Paterra R, Yip S, Petrecca K, Chan JA, Finocchiaro G, Lasorella A, Sanson M, Iavarone A. Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild- type Glioma. Clin Cancer Res. 2015 Jul 15;21(14):3307-17. doi: 10.1158/1078-0432.CCR-14-2199. Epub 2015 Jan 21. PMID: 25609060; PMCID: PMC4506218.
80: Lee WY, Chen KC, Chen HY, Chen CY. Potential mitochondrial isocitrate dehydrogenase R140Q mutant inhibitor from traditional Chinese medicine against cancers. Biomed Res Int. 2014;2014:364625. doi: 10.1155/2014/364625. Epub 2014 Jun 5. PMID: 24995286; PMCID: PMC4066711.
81: Wakimoto H, Tanaka S, Curry WT, Loebel F, Zhao D, Tateishi K, Chen J, Klofas LK, Lelic N, Kim JC, Dias-Santagata D, Ellisen LW, Borger DR, Fendt SM, Vander Heiden MG, Batchelor TT, Iafrate AJ, Cahill DP, Chi AS. Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas. Clin Cancer Res. 2014 Jun 1;20(11):2898-909. doi: 10.1158/1078-0432.CCR-13-3052. Epub 2014 Apr 8. PMID: 24714777; PMCID: PMC4070445.
82: Wang G, Sai K, Gong F, Yang Q, Chen F, Lin J. Mutation of isocitrate dehydrogenase 1 induces glioma cell proliferation via nuclear factor-κB activation in a hypoxia-inducible factor 1-α dependent manner. Mol Med Rep. 2014 May;9(5):1799-805. doi: 10.3892/mmr.2014.2052. Epub 2014 Mar 14. PMID: 24626950.
83: Zhang L, Wang M, Wang W, Mo J. Incidence and prognostic value of multiple gene promoter methylations in gliomas. J Neurooncol. 2014 Jan;116(2):349-56. doi: 10.1007/s11060-013-1301-5. Epub 2013 Nov 6. PMID: 24197988.