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Molecular and Clinical Oncology
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September-2024 Volume 21 Issue 3

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Review Open Access

Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review)

  • Authors:
    • Thenzing J. Silva-Hurtado
    • Julio F. Inocencio
    • Raymund L. Yong
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Leo M. Davidoff Department of Neurosurgery, Montefiore Medical Center, Einstein College of Medicine, Bronx, NY 10461, USA
    Copyright: © Silva-Hurtado et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 59
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    Published online on: June 28, 2024
       https://doi.org/10.3892/mco.2024.2757
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Abstract

DNA hypomethylating agents (HMAs) such as decitabine and 5‑azacytidine have established roles in the treatment paradigms for myelodysplastic syndrome and acute myelogenous leukemia, where they are considered to exert their anticancer effects by restoring the expression of tumor suppressor genes. Due to their relatively favorable adverse effect profile and known ability to pass through the blood‑brain barrier, applications in the treatment of glioblastoma (GBM) and other central nervous system malignancies are under active investigation. The present review examines the types of HMAs currently available, their known and less‑understood antineoplastic mechanisms, and the evidence to date of their preclinical and clinical efficacy in glioblastoma and other solid malignancies. The present review discusses the potential synergies HMAs may have with established and emerging GBM treatments, including temozolomide, immune checkpoint inhibitors and cancer vaccines. Recent successes and setbacks in clinical trials for newly diagnosed and recurrent GBM are summarized in order to highlight opportunities for HMAs to improve therapeutic responses. Challenges for future clinical trials are also assessed.
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1 

Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, et al: Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science. 295:1079–1082. 2002.PubMed/NCBI View Article : Google Scholar

2 

Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, Campos C, Fabius AW, Lu C, Ward PS, et al: IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature. 483:479–483. 2012.PubMed/NCBI View Article : Google Scholar

3 

Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, et al: IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 483:474–478. 2012.PubMed/NCBI View Article : Google Scholar

4 

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, et al: The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro Oncol. 23:1231–1251. 2021.PubMed/NCBI View Article : Google Scholar

5 

Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016-2020. Neuro Oncol. 25 (12 Suppl 2):iv1–iv99. 2023.PubMed/NCBI View Article : Google Scholar

6 

Alnahhas I, Alsawas M, Rayi A, Palmer JD, Raval R, Ong S, Giglio P, Murad MH and Puduvalli V: Characterizing benefit from temozolomide in MGMT promoter unmethylated and methylated glioblastoma: A systematic review and meta-analysis. Neurooncol Adv. 2(vdaa082)2020.PubMed/NCBI View Article : Google Scholar

7 

Szklener K, Mazurek M, Wieteska M, Wacławska M, Bilski M and Mańdziuk S: New directions in the therapy of glioblastoma. Cancers (Basel). 14(5377)2022.PubMed/NCBI View Article : Google Scholar

8 

Handy DE, Castro R and Loscalzo J: Epigenetic modifications: Basic mechanisms and role in cardiovascular disease. Circulation. 123:2145–2156. 2011.PubMed/NCBI View Article : Google Scholar

9 

Ivanova E, Canovas S, Garcia-Martínez S, Romar R, Lopes JS, Rizos D, Sanchez-Calabuig MJ, Krueger F, Andrews S, Perez-Sanz F, et al: DNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes. Clin Epigenetics. 12(64)2020.PubMed/NCBI View Article : Google Scholar

10 

Duncan CG, Grimm SA, Morgan DL, Bushel PR and Bennett BD: NISC Comparative Sequencing Program. Roberts JD, Tyson FL, Merrick BA and Wade PA: Dosage compensation and DNA methylation landscape of the X chromosome in mouse liver. Sci Rep. 8(10138)2018.PubMed/NCBI View Article : Google Scholar

11 

Brabson JP, Leesang T, Mohammad S and Cimmino L: Epigenetic regulation of genomic stability by vitamin C. Front Genet. 12(675780)2021.PubMed/NCBI View Article : Google Scholar

12 

Dhar GA, Saha S, Mitra P and Nag Chaudhuri R: DNA methylation and regulation of gene expression: Guardian of our health. Nucleus (Calcutta). 64:259–270. 2021.PubMed/NCBI View Article : Google Scholar

13 

Compere SJ and Palmiter RD: DNA methylation controls the inducibility of the mouse metallothionein-I gene lymphoid cells. Cell. 25:233–240. 1981.PubMed/NCBI View Article : Google Scholar

14 

Moore LD, Le T and Fan G: DNA methylation and its basic function. Neuropsychopharmacology. 38:23–38. 2013.PubMed/NCBI View Article : Google Scholar

15 

Mortusewicz O, Schermelleh L, Walter J, Cardoso MC and Leonhardt H: Recruitment of DNA methyltransferase I to DNA repair sites. Proc Natl Acad Sci USA. 102:8905–8909. 2005.PubMed/NCBI View Article : Google Scholar

16 

Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E and Sasaki H: Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 429:900–903. 2004.PubMed/NCBI View Article : Google Scholar

17 

Aapola U, Kawasaki K, Scott HS, Ollila J, Vihinen M, Heino M, Shintani A, Kawasaki K, Minoshima S, Krohn K, et al: Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family. Genomics. 65:293–298. 2000.PubMed/NCBI View Article : Google Scholar

18 

Jin B, Li Y and Robertson KD: DNA methylation: Superior or subordinate in the epigenetic hierarchy? Genes Cancer. 2:607–617. 2011.PubMed/NCBI View Article : Google Scholar

19 

Rideout WM III, Coetzee GA, Olumi AF and Jones PA: 5-Methylcytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science. 249:1288–1290. 1990.PubMed/NCBI View Article : Google Scholar

20 

Ramirez-Carrozzi VR, Braas D, Bhatt DM, Cheng CS, Hong C, Doty KR, Black JC, Hoffmann A, Carey M and Smale ST: A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell. 138:114–128. 2009.PubMed/NCBI View Article : Google Scholar

21 

Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, et al: Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 448:553–560. 2007.PubMed/NCBI View Article : Google Scholar

22 

Brenet F, Moh M, Funk P, Feierstein E, Viale AJ, Socci ND and Scandura JM: DNA methylation of the first exon is tightly linked to transcriptional silencing. PLoS One. 6(e14524)2011.PubMed/NCBI View Article : Google Scholar

23 

Hellman A and Chess A: Gene body-specific methylation on the active X chromosome. Science. 315:1141–1143. 2007.PubMed/NCBI View Article : Google Scholar

24 

Bogdanović O and Veenstra GJ: DNA methylation and methyl-CpG binding proteins: Developmental requirements and function. Chromosoma. 118:549–565. 2009.PubMed/NCBI View Article : Google Scholar

25 

Li Y, Zheng H, Wang Q, Zhou C, Wei L, Liu X, Zhang W, Zhang Y, Du Z, Wang X and Xie W: Genome-wide analyses reveal a role of polycomb in promoting hypomethylation of DNA methylation valleys. Genome Biol. 19(18)2018.PubMed/NCBI View Article : Google Scholar

26 

Mohn F, Weber M, Rebhan M, Roloff TC, Richter J, Stadler MB, Bibel M and Schübeler D: Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol Cell. 30:755–766. 2008.PubMed/NCBI View Article : Google Scholar

27 

Ghadiri Moghaddam F, Farajnia S, Karbalaei-Mahdi M and Monir L: Epigenetic insights in the diagnosis, prognosis, and treatment selection in CRC, an updated review. Mol Biol Rep. 49:10013–10022. 2022.PubMed/NCBI View Article : Google Scholar

28 

Collings CK and Anderson JN: Links between DNA methylation and nucleosome occupancy in the human genome. Epigenetics Chromatin. 10(18)2017.PubMed/NCBI View Article : Google Scholar

29 

Huang KK, Ramnarayanan K, Zhu F, Srivastava S, Xu C, Tan ALK, Lee M, Tay S, Das K, Xing M, et al: Genomic and epigenomic profiling of high-risk intestinal metaplasia reveals molecular determinants of progression to gastric cancer. Cancer Cell. 33:137–150.e5. 2018.PubMed/NCBI View Article : Google Scholar

30 

Wang Q, Xiong F, Wu G, Liu W, Chen J, Wang B and Chen Y: Gene body methylation in cancer: Molecular mechanisms and clinical applications. Clin Epigenetics. 14(154)2022.PubMed/NCBI View Article : Google Scholar

31 

Santini V and Ossenkoppele GJ: Hypomethylating agents in the treatment of acute myeloid leukemia: A guide to optimal use. Crit Rev Oncol Hematol. 140:1–7. 2019.PubMed/NCBI View Article : Google Scholar

32 

Holliday R and Ho T: DNA methylation and epigenetic inheritance. Methods. 27:179–183. 2002.PubMed/NCBI View Article : Google Scholar

33 

Jabbour E, Issa JP, Garcia-Manero G and Kantarjian H: Evolution of decitabine development: Accomplishments, ongoing investigations, and future strategies. Cancer. 112:2341–2351. 2008.PubMed/NCBI View Article : Google Scholar

34 

Sorm F and Veselý J: Effect of 5-aza-2'-deoxycytidine against leukemic and hemopoietic tissues in AKR mice. Neoplasma. 15:339–343. 1968.PubMed/NCBI

35 

Xu K and Hansen E: Novel agents for myelodysplastic syndromes. J Oncol Pharm Pract. 27:1982–1992. 2021.PubMed/NCBI View Article : Google Scholar

36 

Kordella C, Lamprianidou E and Kotsianidis I: Mechanisms of action of hypomethylating agents: Endogenous retroelements at the epicenter. Front Oncol. 11(650473)2021.PubMed/NCBI View Article : Google Scholar

37 

Quintás-Cardama A, Santos FP and Garcia-Manero G: Therapy with azanucleosides for myelodysplastic syndromes. Nat Rev Clin Oncol. 7:433–444. 2010.PubMed/NCBI View Article : Google Scholar

38 

Hollenbach PW, Nguyen AN, Brady H, Williams M, Ning Y, Richard N, Krushel L, Aukerman SL, Heise C and MacBeth KJ: A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One. 5(e9001)2010.PubMed/NCBI View Article : Google Scholar

39 

Seelan RS, Mukhopadhyay P, Pisano MM and Greene RM: Effects of 5-Aza-2'-deoxycytidine (decitabine) on gene expression. Drug Metab Rev. 50:193–207. 2018.PubMed/NCBI View Article : Google Scholar

40 

Cashen AF, Shah AK, Todt L, Fisher N and DiPersio J: Pharmacokinetics of decitabine administered as a 3-h infusion to patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Cancer Chemother Pharmacol. 61:759–766. 2008.PubMed/NCBI View Article : Google Scholar

41 

Chabot GG, Rivard GE and Momparler RL: Plasma and cerebrospinal fluid pharmacokinetics of 5-Aza-2'-deoxycytidine in rabbits and dogs. Cancer Res. 43:592–597. 1983.PubMed/NCBI

42 

Kim N, Norsworthy KJ, Subramaniam S, Chen H, Manning ML, Kitabi E, Earp J, Ehrlich LA, Okusanya OO, Vallejo J, et al: FDA approval summary: Decitabine and cedazuridine tablets for myelodysplastic syndromes. Clin Cancer Res. 28:3411–3416. 2022.PubMed/NCBI View Article : Google Scholar

43 

Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O'Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, et al: Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 109:52–57. 2007.PubMed/NCBI View Article : Google Scholar

44 

Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, et al: Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study. Cancer. 106:1794–1803. 2006.PubMed/NCBI View Article : Google Scholar

45 

Müller A and Florek M: 5-Azacytidine/azacitidine. Recent Results Cancer Res. 184:159–170. 2010.PubMed/NCBI View Article : Google Scholar

46 

Krawczyk J, Keane N, Freeman CL, Swords R, O'Dwyer M and Giles FJ: 5-Azacytidine for the treatment of myelodysplastic syndromes. Expert Opin Pharmacother. 14:1255–1268. 2013.PubMed/NCBI View Article : Google Scholar

47 

Glover AB, Leyland-Jones BR, Chun HG, Davies B and Hoth DF: Azacitidine: 10 Years later. Cancer Treat Rep. 71:737–746. 1987.PubMed/NCBI

48 

Kaminskas E, Farrell AT, Wang YC, Sridhara R and Pazdur R: FDA drug approval summary: Azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 10:176–182. 2005.PubMed/NCBI View Article : Google Scholar

49 

Marcucci G, Silverman L, Eller M, Lintz L and Beach CL: Bioavailability of azacitidine subcutaneous versus intravenous in patients with the myelodysplastic syndromes. J Clin Pharmacol. 45:597–602. 2005.PubMed/NCBI View Article : Google Scholar

50 

Garcia-Manero G, Roboz G, Walsh K, Kantarjian H, Ritchie E, Kropf P, O'Connell C, Tibes R, Lunin S, Rosenblat T, et al: Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial. Lancet Haematol. 6:e317–e327. 2019.PubMed/NCBI View Article : Google Scholar

51 

Chuang JC, Warner SL, Vollmer D, Vankayalapati H, Redkar S, Bearss DJ, Qiu X, Yoo CB and Jones PA: S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther. 9:1443–1450. 2010.PubMed/NCBI View Article : Google Scholar

52 

Issa JJ, Roboz G, Rizzieri D, Jabbour E, Stock W, O'Connell C, Yee K, Tibes R, Griffiths EA, Walsh K, et al: Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: A multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol. 16:1099–1110. 2015.PubMed/NCBI View Article : Google Scholar

53 

Ramakrishnan S, Hu Q, Krishnan N, Wang D, Smit E, Granger V, Rak M, Attwood K, Johnson C, Morrison C, et al: Decitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer. Cell Death Dis. 8(3217)2017.PubMed/NCBI View Article : Google Scholar

54 

Li M and Zhang D: DNA methyltransferase-1 in acute myeloid leukaemia: Beyond the maintenance of DNA methylation. Ann Med. 54:2011–2023. 2022.PubMed/NCBI View Article : Google Scholar

55 

Pappalardi MB, Keenan K, Cockerill M, Kellner WA, Stowell A, Sherk C, Wong K, Pathuri S, Briand J, Steidel M, et al: Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nat Cancer. 2:1002–1017. 2021.PubMed/NCBI

56 

Quesnel B and Fenaux P: P15INK4b gene methylation and myelodysplastic syndromes. Leuk Lymphoma. 35:437–443. 1999.PubMed/NCBI View Article : Google Scholar

57 

Daver NG, Maiti A, Kadia TM, Vyas P, Majeti R, Wei AH, Garcia-Manero G, Craddock C, Sallman DA and Kantarjian HM: TP53-mutated myelodysplastic syndrome and acute myeloid leukemia: Biology, current therapy, and future directions. Cancer Discov. 12:2516–2529. 2022.PubMed/NCBI View Article : Google Scholar

58 

Claus R, Hackanson B, Poetsch AR, Zucknick M, Sonnet M, Blagitko-Dorfs N, Hiller J, Wilop S, Brümmendorf TH, Galm O, et al: Quantitative analyses of DAPK1 methylation in AML and MDS. Int J Cancer. 131:E138–E142. 2012.PubMed/NCBI View Article : Google Scholar

59 

Flotho C, Claus R, Batz C, Schneider M, Sandrock I, Ihde S, Plass C, Niemeyer CM and Lübbert M: The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 23:1019–1028. 2009.PubMed/NCBI View Article : Google Scholar

60 

Xie B, Peng F, He F, Cheng Y, Cheng J, Zhou Z and Mao W: DNA methylation influences the CTCF-modulated transcription of RASSF1A in lung cancer cells. Cell Biol Int. 46:1900–1914. 2022.PubMed/NCBI View Article : Google Scholar

61 

Tang Q, Cheng J, Cao X, Surowy H and Burwinkel B: Blood-based DNA methylation as biomarker for breast cancer: A systematic review. Clin Epigenetics. 8(115)2016.PubMed/NCBI View Article : Google Scholar

62 

Cheng W, Jiang Y, Liu C, Shen O, Tang W and Wang X: Identification of aberrant promoter hypomethylation of HOXA10 in ovarian cancer. J Cancer Res Clin Oncol. 136:1221–1227. 2010.PubMed/NCBI View Article : Google Scholar

63 

Ranjan N, Pandey V, Panigrahi MK, Klumpp L, Naumann U and Babu PP: The tumor suppressor MTUS1/ATIP1 modulates tumor promotion in glioma: Association with epigenetics and DNA repair. Cancers (Basel). 13(1245)2021.PubMed/NCBI View Article : Google Scholar

64 

Götze S, Feldhaus V, Traska T, Wolter M, Reifenberger G, Tannapfel A, Kuhnen C, Martin D, Müller O and Sievers S: ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma. BMC Cancer. 9(447)2009.PubMed/NCBI View Article : Google Scholar

65 

Alaminos M, Dávalos V, Ropero S, Setién F, Paz MF, Herranz M, Fraga MF, Mora J, Cheung NK, Gerald WL and Esteller M: EMP3, a myelin-related gene located in the critical 19q13.3 region, is epigenetically silenced and exhibits features of a candidate tumor suppressor in glioma and neuroblastoma. Cancer Res. 65:2565–2571. 2005.PubMed/NCBI View Article : Google Scholar

66 

Sanaei M and Kavoosi F: The effect of 5-aza,2'-deoxyCytidine (5 AZA CdR or decitabine) on extrinsic, intrinsic, and JAK/STAT pathways in neuroblastoma and glioblastoma cells lines. Asian Pac J Cancer Prev. 24:1841–1854. 2023.PubMed/NCBI View Article : Google Scholar

67 

Yang X, Han H, De Carvalho DD, Lay FD, Jones PA and Liang G: Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell. 26:577–590. 2014.PubMed/NCBI View Article : Google Scholar

68 

Ochs K and Kaina B: Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res. 60:5815–5824. 2000.PubMed/NCBI

69 

Tabu K, Sasai K, Kimura T, Wang L, Aoyanagi E, Kohsaka S, Tanino M, Nishihara H and Tanaka S: Promoter hypomethylation regulates CD133 expression in human gliomas. Cell Res. 18:1037–1046. 2008.PubMed/NCBI View Article : Google Scholar

70 

Yi JM, Tsai HC, Glöckner SC, Lin S, Ohm JE, Easwaran H, James CD, Costello JF, Riggins G, Eberhart CG, et al: Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors. Cancer Res. 68:8094–8103. 2008.PubMed/NCBI View Article : Google Scholar

71 

Federici L, Capelle L, Annereau M, Bielle F, Willekens C, Dehais C, Laigle-Donadey F, Hoang-Xuan K, Delattre JY, Idbaih A, et al: 5-Azacitidine in patients with IDH1/2-mutant recurrent glioma. Neuro Oncol. 22:1226–1228. 2020.PubMed/NCBI View Article : Google Scholar

72 

Sato T, Issa JJ and Kropf P: DNA Hypomethylating drugs in cancer therapy. Cold Spring Harb Perspect Med. 7(a026948)2017.PubMed/NCBI View Article : Google Scholar

73 

Matei D, Fang F, Shen C, Schilder J, Arnold A, Zeng Y, Berry WA, Huang T and Nephew KP: Epigenetic resensitization to platinum in ovarian cancer. Cancer Res. 72:2197–2205. 2012.PubMed/NCBI View Article : Google Scholar

74 

Glaysher S, Gabriel FG, Johnson P, Polak M, Knight LA, Parker K, Poole M, Narayanan A and Cree IA: NHS Collaborative Research Programme for Predictive Oncology. Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy. Br J Cancer. 103:656–662. 2010.PubMed/NCBI View Article : Google Scholar

75 

Hannon CE and Eisen MB: Intrinsic protein disorder is insufficient to drive subnuclear clustering in embryonic transcription factors. Elife. 12(RP88221)2024.PubMed/NCBI View Article : Google Scholar

76 

Moen EL, Stark AL, Zhang W, Dolan ME and Godley LA: The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide. Mol Cancer Ther. 13:1334–1344. 2014.PubMed/NCBI View Article : Google Scholar

77 

Plumb JA, Strathdee G, Sludden J, Kaye SB and Brown R: Reversal of drug resistance in human tumor xenografts by 2'-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res. 60:6039–6044. 2000.PubMed/NCBI

78 

Tawbi HA, Beumer JH, Tarhini AA, Moschos S, Buch SC, Egorin MJ, Lin Y, Christner S and Kirkwood JM: Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: A phase I/II study and pharmacokinetic analysis. Ann Oncol. 24:1112–1119. 2013.PubMed/NCBI View Article : Google Scholar

79 

Skiriutė D, Vaitkienė P, Ašmonienė V, Steponaitis G, Deltuva VP and Tamašauskas A: Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma. J Neurooncol. 113:441–449. 2013.PubMed/NCBI View Article : Google Scholar

80 

Rodríguez-Hernández I, Garcia JL, Santos-Briz A, Hernández-Laín A, González-Valero JM, Gómez-Moreta JA, Toldos-González O, Cruz JJ, Martin-Vallejo J and González-Sarmiento R: Integrated analysis of mismatch repair system in malignant astrocytomas. PLoS One. 8(e76401)2013.PubMed/NCBI View Article : Google Scholar

81 

Fukushima T, Katayama Y, Watanabe T, Yoshino A, Ogino A, Ohta T and Komine C: Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea. Clin Cancer Res. 11:1539–1544. 2005.PubMed/NCBI View Article : Google Scholar

82 

Gallitto M, Cheng He R, Inocencio JF, Wang H, Zhang Y, Deikus G, Wasserman I, Strahl M, Smith M, Sebra R and Yong RL: Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1. J Neurooncol. 147:557–566. 2020.PubMed/NCBI View Article : Google Scholar

83 

Mehnert JM, Panda A, Zhong H, Hirshfield K, Damare S, Lane K, Sokol L, Stein MN, Rodriguez-Rodriquez L, Kaufman HL, et al: Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer. J Clin Invest. 126:2334–2340. 2016.PubMed/NCBI View Article : Google Scholar

84 

Panda A, Betigeri A, Subramanian K, Ross JS, Pavlick DC, Ali S, Markowski P, Silk A, Kaufman HL, Lattime E, et al: Identifying a clinically applicable mutational burden threshold as a potential biomarker of response to immune checkpoint therapy in solid tumors. JCO Precis Oncol. 2017(PO.17.00146)2017.PubMed/NCBI View Article : Google Scholar

85 

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al: Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 348:124–128. 2015.PubMed/NCBI View Article : Google Scholar

86 

DeCordova S, Shastri A, Tsolaki AG, Yasmin H, Klein L, Singh SK and Kishore U: Molecular heterogeneity and immunosuppressive microenvironment in glioblastoma. Front Immunol. 11(1402)2020.PubMed/NCBI View Article : Google Scholar

87 

Zaidi N and Jaffee EM: Immune cells track hard-to-target brain tumours. Nature. 565:170–171. 2019.PubMed/NCBI View Article : Google Scholar

88 

Zhong J, Yang X, Chen J, He K, Gao X, Wu X, Zhang M, Zhou H, Xiao F, An L, et al: Circular EZH2-encoded EZH2-92aa mediates immune evasion in glioblastoma via inhibition of surface NKG2D ligands. Nat Commun. 13(4795)2022.PubMed/NCBI View Article : Google Scholar

89 

Long S, Huang G, Ouyang M, Xiao K, Zhou H, Hou A, Li Z, Zhong Z, Zhong D, Wang Q, et al: Epigenetically modified AP-2α by DNA methyltransferase facilitates glioma immune evasion by upregulating PD-L1 expression. Cell Death Dis. 14(365)2023.PubMed/NCBI View Article : Google Scholar

90 

Tompa M, Kraboth Z, Galik B, Kajtar B, Gyenesei A and Kalman B: Epigenetic suppression of the IL-7 pathway in progressive glioblastoma. Biomedicines. 10(2174)2022.PubMed/NCBI View Article : Google Scholar

91 

Héninger E, Krueger TE and Lang JM: Augmenting antitumor immune responses with epigenetic modifying agents. Front Immunol. 6(29)2015.PubMed/NCBI View Article : Google Scholar

92 

Malekzadeh P, Pasetto A, Robbins PF, Parkhurst MR, Paria BC, Jia L, Gartner JJ, Hill V, Yu Z, Restifo NP, et al: Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers. J Clin Invest. 129:1109–1114. 2019.PubMed/NCBI View Article : Google Scholar

93 

Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, et al: T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med. 375:2255–2262. 2016.PubMed/NCBI View Article : Google Scholar

94 

Ma R, Rei M, Woodhouse I, Ferris K, Kirschner S, Chandran A, Gileadi U, Chen JL, Pereira Pinho M, Ariosa-Morejon Y, et al: Decitabine increases neoantigen and cancer testis antigen expression to enhance T-cell-mediated toxicity against glioblastoma. Neuro Oncol. 24:2093–2106. 2022.PubMed/NCBI View Article : Google Scholar

95 

Okemoto K, Kasai K, Wagner B, Haseley A, Meisen H, Bolyard C, Mo X, Wehr A, Lehman A, Fernandez S, et al: DNA demethylating agents synergize with oncolytic HSV1 against malignant gliomas. Clin Cancer Res. 19:5952–5959. 2013.PubMed/NCBI View Article : Google Scholar

96 

Nebhan CA and Johnson DB: Pembrolizumab in the adjuvant treatment of melanoma: Efficacy and safety. Expert Rev Anticancer Ther. 21:583–590. 2021.PubMed/NCBI View Article : Google Scholar

97 

Allen PB, Savas H, Evens AM, Advani RH, Palmer B, Pro B, Karmali R, Mou E, Bearden J, Dillehay G, et al: Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood. 137:1318–1326. 2021.PubMed/NCBI View Article : Google Scholar

98 

Nie J, Wang C, Liu Y, Yang Q, Mei Q, Dong L, Li X, Liu J, Ku W, Zhang Y, et al: Addition of low-dose decitabine to anti-PD-1 antibody camrelizumab in relapsed/refractory classical hodgkin lymphoma. J Clin Oncol. 37:1479–1489. 2019.PubMed/NCBI View Article : Google Scholar

99 

Merseburger AS, Apolo AB, Chowdhury S, Hahn NM, Galsky MD, Milowsky MI, Petrylak D, Powles T, Quinn DI, Rosenberg JE, et al: SIU-ICUD recommendations on bladder cancer: Systemic therapy for metastatic bladder cancer. World J Urol. 37:95–105. 2019.PubMed/NCBI View Article : Google Scholar

100 

Chowdhury S, Infante JR, Hawkins R, Voss MH, Perini R, Arkenau T, Voskoboynik M, Aimone P, Naeije I, Reising A and McDermott DF: A phase I/II study to assess the safety and efficacy of pazopanib and pembrolizumab combination therapy in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 19:434–446. 2021.PubMed/NCBI View Article : Google Scholar

101 

Ghoneim HE, Fan Y, Moustaki A, Abdelsamed HA, Dash P, Dogra P, Carter R, Awad W, Neale G, Thomas PG and Youngblood B: De novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation. Cell. 170:142–157.e19. 2017.PubMed/NCBI View Article : Google Scholar

102 

Li X, Li Y, Dong L, Chang Y, Zhang X, Wang C, Chen M, Bo X, Chen H, Han W and Nie J: Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models. J Clin Invest. 133(e165673)2023.PubMed/NCBI View Article : Google Scholar

103 

Wang Y, Tong C, Dai H, Wu Z, Han X, Guo Y, Chen D, Wei J, Ti D, Liu Z, et al: Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming. Nat Commun. 12(409)2021.PubMed/NCBI View Article : Google Scholar

104 

Papadatos-Pastos D, Yuan W, Pal A, Crespo M, Ferreira A, Gurel B, Prout T, Ameratunga M, Chénard-Poirier M, Curcean A, et al: Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors. J Immunother Cancer. 10(e004495)2022.PubMed/NCBI View Article : Google Scholar

105 

Wei SC, Duffy CR and Allison JP: Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 8:1069–1086. 2018.PubMed/NCBI View Article : Google Scholar

106 

Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr O, et al: Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma: The CheckMate 143 phase 3 randomized clinical trial. JAMA Oncol. 6:1003–1010. 2020.PubMed/NCBI View Article : Google Scholar

107 

Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bähr O, et al: Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 25:123–134. 2023.PubMed/NCBI View Article : Google Scholar

108 

Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, et al: Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 24:1935–1949. 2022.PubMed/NCBI View Article : Google Scholar

109 

Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanović S, Gouttefangeas C, Platten M, Tabatabai G, Dutoit V, van der Burg SH, et al: Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 565:240–245. 2019.PubMed/NCBI View Article : Google Scholar

110 

Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, et al: Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 565:234–239. 2019.PubMed/NCBI View Article : Google Scholar

111 

Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, Lihm J, Ceglia N, Guasp P, Chu A, et al: Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 618:144–150. 2023.PubMed/NCBI View Article : Google Scholar

112 

Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, et al: Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): A randomised, double-blind, international phase 3 trial. Lancet Oncol. 18:1373–1385. 2017.PubMed/NCBI View Article : Google Scholar

113 

Zhao T, Cai Y, Jiang Y, He X, Wei Y, Yu Y and Tian X: Vaccine adjuvants: Mechanisms and platforms. Signal Transduct Target Ther. 8(283)2023.PubMed/NCBI View Article : Google Scholar

114 

Palucka K and Banchereau J: Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 12:265–277. 2012.PubMed/NCBI View Article : Google Scholar

115 

Liau LM, Ashkan K, Brem S, Campian JL, Trusheim JE, Iwamoto FM, Tran DD, Ansstas G, Cobbs CS, Heth JA, et al: Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: A phase 3 prospective externally controlled cohort trial. JAMA Oncol. 9:112–121. 2023.PubMed/NCBI View Article : Google Scholar

116 

Everson RG, Antonios JP, Lisiero DN, Soto H, Scharnweber R, Garrett MC, Yong WH, Li N, Li G, Kruse CA, et al: Efficacy of systemic adoptive transfer immunotherapy targeting NY-ESO-1 for glioblastoma. Neuro Oncol. 18:368–378. 2016.PubMed/NCBI View Article : Google Scholar

117 

Zhang X, Rao A, Sette P, Deibert C, Pomerantz A, Kim WJ, Kohanbash G, Chang Y, Park Y, Engh J, et al: IDH mutant gliomas escape natural killer cell immune surveillance by downregulation of NKG2D ligand expression. Neuro Oncol. 18:1402–1412. 2016.PubMed/NCBI View Article : Google Scholar

118 

Zhang X, Kim WJ, Rao AV, Jaman E, Deibert CP, Sandlesh P, Krueger K, Allen JC and Amankulor NM: In vivo efficacy of decitabine as a natural killer cell-mediated immunotherapy against isocitrate dehydrogenase mutant gliomas. Neurosurg Focus. 52(E3)2022.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Silva-Hurtado TJ, Inocencio JF and Yong RL: Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review). Mol Clin Oncol 21: 59, 2024.
APA
Silva-Hurtado, T.J., Inocencio, J.F., & Yong, R.L. (2024). Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review). Molecular and Clinical Oncology, 21, 59. https://doi.org/10.3892/mco.2024.2757
MLA
Silva-Hurtado, T. J., Inocencio, J. F., Yong, R. L."Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review)". Molecular and Clinical Oncology 21.3 (2024): 59.
Chicago
Silva-Hurtado, T. J., Inocencio, J. F., Yong, R. L."Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review)". Molecular and Clinical Oncology 21, no. 3 (2024): 59. https://doi.org/10.3892/mco.2024.2757
Copy and paste a formatted citation
x
Spandidos Publications style
Silva-Hurtado TJ, Inocencio JF and Yong RL: Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review). Mol Clin Oncol 21: 59, 2024.
APA
Silva-Hurtado, T.J., Inocencio, J.F., & Yong, R.L. (2024). Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review). Molecular and Clinical Oncology, 21, 59. https://doi.org/10.3892/mco.2024.2757
MLA
Silva-Hurtado, T. J., Inocencio, J. F., Yong, R. L."Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review)". Molecular and Clinical Oncology 21.3 (2024): 59.
Chicago
Silva-Hurtado, T. J., Inocencio, J. F., Yong, R. L."Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review)". Molecular and Clinical Oncology 21, no. 3 (2024): 59. https://doi.org/10.3892/mco.2024.2757
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