Glioblastoma - actual knowledge and future perspectives Review article
Article Sidebar
Published:
Jun 30, 2022
Keywords:
glioblastoma multiforme, oncology, miRNA, pathogenesis
Main Article Content
Abstract
Glioblastoma is the most severe IV-class glioma and therefore the prognosis for patients remains poor despite some improvement in the treatment area. The neurological or psychiatric symptoms especially fast-developing ones should be fully investigated. This article aims to summarize actual knowledge of glioblastoma and present future perspectives. The underlying causes are usually associated with mutations of EGFR, PTEN, IDH1, p53 genes. The MRI scan, MGMT promoter methylation status, GFAP immunohistochemical detection and Karnofsky performance status are valuable diagnostic tools and some other potential biomarkers with high specificity are proposed. The standard of care is surgery and Stupp protocol which is the combination of radiotherapy and chemotherapy with temozolomide. Nevertheless, after remission the treatment possibilities are limited. Many efforts have been devoted to elaborate novel therapeutic strategies using e.g. CAR-T cells, nanoparticles, monoclonal antibodies, miRNA, siRNA or proteasome inhibitors.
Downloads
Download data is not yet available.
Metrics
Metrics Loading ...
Article Details
How to Cite
1.
Bilicki D, Zbrożek M, Fudalej M, Deptała A, Badowska-Kozakiewicz A. Glioblastoma - actual knowledge and future perspectives. OncoReview [Internet]. 2022Jun.30 [cited 2024Nov.24];12(2(46):35-4. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/1795
Issue
Section
PERSONALIZED ONCOLOGY
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
1. Piccirillo SGM, Colman S, Potter NE et al. Genetic and functional diversity of propagating cells in glioblastoma. Stem Cell Reports. 2015; 4 (1): 7-15.
2. Gallego O. Nonsurgical treatment of recurrent glioblastoma. Curr Oncol. 2015; 22(4): e273-281.
3. Adamson C, Kanu OO, Mehta AI et al. Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009; 18(8): 1061-83.
4. Taylor OG, Brzozowski JS, Skelding KA. Glioblastoma Multiforme: An Overview of Emerging Therapeutic Targets. Front Oncol. 2019; 9: 963.
5. Ostrom QT, Patil N, Cioffi G et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013-2017. Neuro Oncol. 2020; 22(12 suppl 2): iv1-iv96.
6. Batash R, Asna N, Schaffer P et al. Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review. Curr Med Chem. 2017; 24 (27): 3002-9.
7. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013; 19(4): 764-72.
8. Ludwig K, Kornblum HI. Molecular markers in glioma. J Neurooncol. 2017; 134(3): 505-12.
9. Kim CK, Nguyen TL, Joo KM et al. Negative regulation of p53 by the long isoform of ErbB3 binding protein Ebp1 in brain tumors. Cancer Res. 2010; 70(23): 9730-41.
10. Soomro SH, Ting LR, Qing YY et al. Molecular biology of glioblastoma: Classification and mutational locations. J Pak Med Assoc. 2017; 67(9): 1410-4.
11. Verhaak RG, Hoadley KA, Purdom E et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17(1): 98-110.
12. Alifieris C, Trafalis DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther. 2015; 152: 63-82.
13. Huang Z, Cheng L, Guryanova OA et al. Cancer stem cells in glioblastoma-molecular signaling and therapeutic targeting. Protein Cell. 2010; 1(7): 638-55.
14. Alexander BM, Cloughesy TF. Adult Glioblastoma. J Clin Oncol. 2017; 35 (21): 2402-9.
15. Khandwala K, Mubarak F, Minhas K. The many faces of glioblastoma: Pictorial review of atypical imaging features. Neuroradiol J. 2021; 34(1): 33-41.
16. Cunha M, Maldaun MVC. Metastasis from glioblastoma multiforme: a meta-analysis. Rev Assoc Med Bras. 2019; 65(3): 424-33.
17. Lee EJ, Ahn KJ, Lee EK et al. Potential role of advanced MRI techniques for the peritumoural region in differentiating glioblastoma multiforme and solitary metastatic lesions. Clin Radiol. 2013; 68 (12): e689-697.
18. Nabors LB, Portnow J, Ammirati M et al. Central Nervous System Cancers, Version 1.2015. J Natl Compr Canc Netw. 2015; 13(10): 1191-202.
19. Staller A. Presumed Glioblastoma Multiforme: A Case for Biopsy Prior to Treatment. Clin J Oncol Nurs. 2016; 20(1): 95-7.
20. Figueroa JM, Carter BS. Detection of glioblastoma in biofluids. J Neurosurg. 2018; 129 (2): 334-40.
21. Quddusi A, Shamim MS. Serum biomarkers for glioblastoma multiforme. J Pak Med Assoc. 2019; 69(6): 913-4.
22. Ostrom QT, Bauchet L, Davis FG et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro-Oncology. 2014; 16(7): 896-913.
23. Ellor SV, Pagano-Young TA, Avgeropoulos NG. Glioblastoma: background, standard treatment paradigms, and supportive care considerations. J Law Med Ethics. 2014; 42(2): 171-82.
24. Stummer W, Pichlmeier U, Meinel T et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006; 7(5): 392-401.
25. Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med. 2005; 352(10): 987-96.
26. Stupp R, Taillibert S, Kanner A et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017; 318(23): 2306-16.
27. Ameratunga M, Pavlakis N, Wheeler H et al. Anti-angiogenic therapy for high-grade glioma. Cochrane Database Syst Rev. 2018; 11(11): CD008218- CD008218.
28. Stevens GH. Antiepileptic therapy in patients with central nervous system malignancies. Curr Neurol Neurosci Rep. 2006; 6(4): 311-8.
29. Shao M, Liu W, Wang Y. Differentially expressed LncRNAs as potential prognostic biomarkers for glioblastoma. Cancer Genetics. 2018; 226-7: 23-9.
30. Chen HH, Zong J, Wang SJ. LncRNA GAPLINC promotes the growth and metastasis of glioblastoma by sponging miR-331-3p. Eur Rev Med Pharmacol Sci. 2019; 23(1): 262-70.
31. Li J, Ji X, Wang H. Targeting Long Noncoding RNA HMMR-AS1 Suppresses and Radiosensitizes Glioblastoma. Neoplasia. 2018; 20(5): 456-66.
32. Li Q, Dong C, Cui J et al. Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme. J Exp Clin Cancer Res. 2018; 37(1): 265.
33. Tang G, Luo L, Zhang J et al. lncRNA LINC01057 promotes mesenchymal differentiation by activating NF-κB signaling in glioblastoma. Cancer Letters. 2021; 498: 152-64.
34. Baspinar Y, Elmaci I, Ozpinar A et al. Long non-coding RNA MALAT1 as a key target in pathogenesis of glioblastoma. Janus faces or Achilles’ heal? Gene. 2020; 739: 144518.
35. Liao K, Lin Y, Gao W et al. Blocking lncRNA MALAT1/miR-199a/ZHX1 Axis Inhibits Glioblastoma Proliferation and Progression. Molecular Therapy – Nucleic Acids. 2019; 18: 388-99.
36. Li Z, Zhang J, Zheng H et al. Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib, overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme. J Exp Clin Cancer Res. 2019; 38(1): 380.
37. Ren J, Yang Y, Xue J et al. Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095. Biochem Biophys Res Commun. 2018; 496(2): 712-8.
38. Mazor G, Levin L, Picard D et al. The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells. Cell Death Dis. 2019; 10(3): 246.
39. Andrews LP, Yano H, Vignali DAA. Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups. Nat Immunol. 2019; 20(11): 1425-34.
40. Sabahi M, Jabbari P, Alizadeh Haghighi M et al. Proposing a tandem AND-gate CAR T cell targeting glioblastoma multiforme. Med Hypotheses. 2020; 137: 109559.
41. Aguilar B, Sarkissian A, Brito A et al. 275. Optimization of IL13Rα2-Specific CAR T Cells for Clinical Development Using Orthotopic Human Glioblastoma Models in NSG Mice. Mol Ther. 2016; 24: S109.
42. Keskin DB, Anandappa AJ, Sun J et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019; 565(7738): 234-9.
43. Burger MC, Zhang C, Harter PN et al. CAR-Engineered NK Cells for the Treatment of Glioblastoma: Turning Innate Effectors Into Precision Tools for Cancer Immunotherapy. Front Immunol. 2019; 10: 2683.
44. Peereboom D, Nabors LB, Kumthekar P et al. 373O – Results of phase II trial of SL-701, a novel immunotherapy targeting IL-13Ra2, EphA2, and survivin, in adults with second-line recurrent glioblastoma (GBM). Ann Oncol. 2018; 29: viii122-viii123.
45. Gardell JL, Matsumoto LR, Chinn H et al. Human macrophages engineered to secrete a bispecific T cell engager support antigen-dependent T cell responses to glioblastoma. J Immunother Cancer. 2020; 8(2): e001202.
46. Cui J, Wang H, Medina R et al. Inhibition of PP2A with LB-100 Enhances Efficacy of CAR-T Cell Therapy Against Glioblastoma. Cancers (Basel). 2020; 12(1):139.
47. Do AS-MS, Amano T, Edwards LA et al. CD133 mRNA-Loaded Dendritic Cell Vaccination Abrogates Glioma Stem Cell Propagation in Humanized Glioblastoma Mouse Model. Mol Ther – Oncolytics. 2020; 18: 295-303.
48. Jin L, Ge H, Long Y et al. CD70, a novel target of CAR T-cell therapy for gliomas. Neuro Oncol. 2018; 20(1): 55-65.
49. Pellegatta S, Savoldo B, Su C et al. 507. Chondroitin Sulfate Proteoglycan 4 (CSPG4)-Redirected T Cells Eliminate Glioblastoma-Derived Neurospheres. Mol Ther. 2016; 24: S202.
50. Jung IY, Kim YY , Yu HS et al. CRISPR/Cas9-Mediated Knockout of DGK Improves Antitumor Activities of Human T Cells. Cancer Res. 2018; 78(16): 4692-703.
51. O'Rourke DM, Nasrallah MP, Desai A et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017; 9(399): eaaa0984
52. Nakazawa T, Natsume A, Nishimura F et al. Effect of CRISPR/Cas9-Mediated PD-1-Disrupted Primary Human Third-Generation CAR-T Cells Targeting EGFRvIII on In Vitro Human Glioblastoma Cell Growth. Cells. 2020; 9(4): 998.
53. Choi BD, Yu X, Castano AP et al. CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma. J Immunother Cancer. 2019; 7(1): 304.
54. Liuzzi AR, Agliardi G, Becher B et al. 106P – A Single Dose of Local IL-12 Promotes Anti-Tumor Effect of Anti-EGFRvIII-CAR-T Cells in a Syngeneic Murine Model of Glioblastoma. Ann Oncol. 2019; 30: xi40.
55. Song Y, Liu Q, Zuo T et al. Combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model. Cell Immunol. 2020; 352: 104112.
56. Ahmed N, Brawley V, Hegde M et al. HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2017; 3(8): 1094-101.
57. Sanber K, Nawas Z, Salsman V et al. Modulation of inhibitory receptor signaling pathways improves CAR T cell activity against glioblastoma. Cytotherapy. 2020; 22(5 suppl): S19-S20.
58. Brown CE, Alizadeh D, Starr R et al. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016; 375(26): 2561-9.
59. Kim GB, Aragon-Sanabria V, Randolph L et al. High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma. Bioact Mater. 2020; 5(3): 624-35.
60. Møller HG, Rasmussen AP, Andersen HH et al. A Systematic Review of MicroRNA in Glioblastoma Multiforme: Micro-modulators in the Mesenchymal Mode of Migration and Invasion. Mol Neurobiol. 2013; 47(1): 131-44.
61. Marino A, Almici E, Migliorin S et al. Piezoelectric barium titanate nanostimulators for the treatment of glioblastoma multiforme. J Colloid Interface Sci. 2019; 538: 449-61.
62. Li T-F, Li K, Zhang Q et al. Dendritic cell-mediated delivery of doxorubicin-polyglycerol-nanodiamond composites elicits enhanced anti-cancer immune response in glioblastoma. Biomaterials. 2018; 181: 35-52.
63. Banerjee I, De K, Mukherjee D et al. Paclitaxel-loaded solid lipid nanoparticles modified with Tyr-3-octreotide for enhanced anti-angiogenic and antiglioma therapy. Acta Biomater. 2016; 38: 69-81.
64. Wu S-Q, Yang C-X, Yan X-P. A Dual-Functional Persistently Luminescent Nanocomposite Enables Engineering of Mesenchymal Stem Cells for Homing and Gene Therapy of Glioblastoma. Adv Funct Mater. 2017; 27(11): 1604992.
65. Roth P, Mason WP, Richardson PG et al. Proteasome inhibition for the treatment of glioblastoma. Expert Opin Investig Drugs. 2020; 29(10): 1133-41.
66. Rahman MA, Gras Navarro A, Brekke J et al. Bortezomib administered prior to temozolomide depletes MGMT, chemosensitizes glioblastoma with unmethylated MGMT promoter and prolongs animal survival. Br J Cancer. 2019; 121(7): 545-55.
67. Cloughesy TF, Mochizuki AY, Orpilla JR et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019; 25(3): 477-86.
68. Guetta-Terrier C, Akosmam B, Chen JS et al. 185 Poster – Antibody blockade resets Chi3L1-induced glioma stem cell phenotypic transitions and reduces glioblastoma tumor burden. Eur J Cancer. 2020; 138: S52.
69. Westphal M, Heese O, Steinbach JP et al. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer. 2015; 51(4): 522-32.
70. Harris-Bookman S, Mathios D, Martin AM et al. Expression of LAG-3 and efficacy of combination treatment with anti-LAG-3 and anti-PD-1 monoclonal antibodies in glioblastoma. Int J Cancer. 2018; 143(12): 3201-8.
71. Arnold AE, Malek-Adamian E, Le PU et al. Antibody-Antisense Oligonucleotide Conjugate Downregulates a Key Gene in Glioblastoma Stem Cells. Mol Ther Nucleic Acids. 2018; 11: 518-27.
72. Lu X, Wang M, Qiang J et al. Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR 379–5p/MAP3K2 axis. Eur J Pharmacol. 2019; 863: 172643.
73. Memari E, Maghsoudi A, Yazdian F et al. Synthesis of PHB-co-PEI nanoparticles as gene carriers for miR-128-encoding plasmid delivery to U87 glioblastoma cells. Colloids Surf A: Physicochem Eng Asp. 2020; 599: 124898.
74. Singh A, Srivastava N, Yadav A et al. Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma. Neoplasia. 2020; 22(10): 497-510.
75. Pan C-M, Chan K-H, Chen C-H et al. MicroRNA-7 targets T-Box 2 to inhibit epithelial-mesenchymal transition and invasiveness in glioblastoma multiforme. Cancer Lett. 2020; 493: 133-42.
76. Rezaei T, Hejazi M, Mansoori B et al. microRNA-181a mediates the chemo-sensitivity of glioblastoma to carmustine and regulates cell proliferation, migration, and apoptosis. Eur J Pharmacol. 2020; 888: 173483.
77. Zhang Y-X, Li X-F, Yuan G-Q et al. β-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G2/M phase transition. J Biol Chem. 2017; 292(21): 8933-47.
78. Wang S, Fan Y, Xu Y et al. GDNFOS1 knockdown decreases the invasion and viability of glioblastoma cells. Exp Ther Med. 2019; 18(2): 1315-22.
79. Lu YJ, Lan YH, Chuang CC et al. Injectable Thermo-Sensitive Chitosan Hydrogel Containing CPT-11-Loaded EGFR-Targeted Graphene Oxide and SLP2
shRNA for Localized Drug/Gene Delivery in Glioblastoma Therapy. Int J Mol Sci. 2020; 21(19): 7111.
80. Lee JA, Ayat N, Sun Z et al. Improving Radiation Response in Glioblastoma Using ECO Nanoparticle Delivery of siRNA Targeting DNA Damage Repair. Int J Radiat Oncol Biol Phys. 2017; 99(2 Suppl): E604.
81. Azambuja JH, Schuh RS, Michels LR et al. Blockade of CD73 delays glioblastoma growth by modulating the immune environment. Cancer Immunol Immunother. 2020; 69(9): 1801-12.
82. Danhier F, Messaoudi K, Lemaire L et al. Combined anti-Galectin-1 and anti-EGFR siRNA-loaded chitosan-lipid nanocapsules decrease temozolomide resistance in glioblastoma: In vivo evaluation. Int J Pharm. 2015; 481(1): 154-61.
83. Ding X, Deng G, Liu J et al. GOLM1 silencing inhibits the proliferation and motility of human glioblastoma cells via the Wnt/β-catenin signaling pathway. Brain Res. 2019; 1717: 117-26.
84. Önay Uçar E, Şengelen A. Resveratrol and siRNA in combination reduces Hsp27 expression and induces caspase-3 activity in human glioblastoma cells. Cell Stress Chaperones. 2019; 24(4): 763-75.
85. Wei J, Marisetty A, Schrand B et al. Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target. J Clin Invest. 2019; 129(1): 137-49.
86. Zheng M, Liu Y, Wang Y et al. ROS-Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy. Adv Mater. 2019; 31(37): e1903277.
87. Cen B, Wei Y, Huang W et al. An Efficient Bivalent Cyclic RGD-PIK3CB siRNA Conjugate for Specific Targeted Therapy against Glioblastoma In Vitro and In Vivo. Mol Ther Nucleic Acids. 2018; 13: 220-32.
88. Esposito CL, Nuzzo S, Catuogno S et al. STAT3 Gene Silencing by Aptamer-siRNA Chimera as Selective Therapeutic for Glioblastoma. Mol Ther Nucleic Acids. 2018; 10: 398-411.
89. Wu S, Luo C, Hameed NUF et al. UCP2 silencing in glioblastoma reduces cell proliferation and invasiveness by inhibiting p38 MAPK pathway. Exp Cell Res. 2020; 394(1): 112110.
90. Yang J, Zhang Q, Liu Y et al. Nanoparticle-based co-delivery of siRNA and paclitaxel for dual-targeting of glioblastoma. Nanomedicine (Lond). 2020; 15(14): 1391-409.
91. Rosenthal M, Clement PM, Campone M et al. Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. ESMO Open. 2020; 5(4): e000672.
92. Das A, Cheng RR, Hilbert ML et al. Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG ROS1 Fusion-Positive Glioblastoma. Cancer Growth Metastasis. 2015; 8: 51-60.
93. Zhu Y-G, Lv Y-X, Guo C-Y et al. Harmine inhibits the proliferation and migration of glioblastoma cells via the FAK/AKT pathway. Life Sci. 2021; 270: 119112.
94. Weller J, Tzaridis T, Mack F et al. Health-related quality of life and neurocognitive functioning with lomustine temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2019; 20(10): 1444-53.
95. Zielke S, Meyer N, Mari M et al. Loperamide, pimozide, and STF-62247 trigger autophagy-dependent cell death in glioblastoma cells. Cell Death Dis. 2018; 9(10): 994.
96. da Fonseca CO, Simão M, Lins IR et al. Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma. J Cancer Res Clin Oncol. 2011; 137(2): 287-93.
97. Sachdeva R, Wu M, Smiljanic S et al. ID1 Is Critical for Tumorigenesis and Regulates Chemoresistance in Glioblastoma. Cancer Res. 2019; 79(16): 4057-71.
98. Biau J, Thivat E, Chautard E et al. Phase 1 trial of ralimetinib (LY 2228820) with radiotherapy plus concomitant temozolomide in the treatment of newly diagnosed glioblastoma. Radiother Oncol. 2021; 154: 227-34.
99. Detti B, Scoccianti S, Lucidi S et al. Regorafenib in glioblastoma recurrence: A case report. Cancer Treat Res Commun. 2021; 26: 100263.
2. Gallego O. Nonsurgical treatment of recurrent glioblastoma. Curr Oncol. 2015; 22(4): e273-281.
3. Adamson C, Kanu OO, Mehta AI et al. Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009; 18(8): 1061-83.
4. Taylor OG, Brzozowski JS, Skelding KA. Glioblastoma Multiforme: An Overview of Emerging Therapeutic Targets. Front Oncol. 2019; 9: 963.
5. Ostrom QT, Patil N, Cioffi G et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013-2017. Neuro Oncol. 2020; 22(12 suppl 2): iv1-iv96.
6. Batash R, Asna N, Schaffer P et al. Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review. Curr Med Chem. 2017; 24 (27): 3002-9.
7. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013; 19(4): 764-72.
8. Ludwig K, Kornblum HI. Molecular markers in glioma. J Neurooncol. 2017; 134(3): 505-12.
9. Kim CK, Nguyen TL, Joo KM et al. Negative regulation of p53 by the long isoform of ErbB3 binding protein Ebp1 in brain tumors. Cancer Res. 2010; 70(23): 9730-41.
10. Soomro SH, Ting LR, Qing YY et al. Molecular biology of glioblastoma: Classification and mutational locations. J Pak Med Assoc. 2017; 67(9): 1410-4.
11. Verhaak RG, Hoadley KA, Purdom E et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17(1): 98-110.
12. Alifieris C, Trafalis DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther. 2015; 152: 63-82.
13. Huang Z, Cheng L, Guryanova OA et al. Cancer stem cells in glioblastoma-molecular signaling and therapeutic targeting. Protein Cell. 2010; 1(7): 638-55.
14. Alexander BM, Cloughesy TF. Adult Glioblastoma. J Clin Oncol. 2017; 35 (21): 2402-9.
15. Khandwala K, Mubarak F, Minhas K. The many faces of glioblastoma: Pictorial review of atypical imaging features. Neuroradiol J. 2021; 34(1): 33-41.
16. Cunha M, Maldaun MVC. Metastasis from glioblastoma multiforme: a meta-analysis. Rev Assoc Med Bras. 2019; 65(3): 424-33.
17. Lee EJ, Ahn KJ, Lee EK et al. Potential role of advanced MRI techniques for the peritumoural region in differentiating glioblastoma multiforme and solitary metastatic lesions. Clin Radiol. 2013; 68 (12): e689-697.
18. Nabors LB, Portnow J, Ammirati M et al. Central Nervous System Cancers, Version 1.2015. J Natl Compr Canc Netw. 2015; 13(10): 1191-202.
19. Staller A. Presumed Glioblastoma Multiforme: A Case for Biopsy Prior to Treatment. Clin J Oncol Nurs. 2016; 20(1): 95-7.
20. Figueroa JM, Carter BS. Detection of glioblastoma in biofluids. J Neurosurg. 2018; 129 (2): 334-40.
21. Quddusi A, Shamim MS. Serum biomarkers for glioblastoma multiforme. J Pak Med Assoc. 2019; 69(6): 913-4.
22. Ostrom QT, Bauchet L, Davis FG et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro-Oncology. 2014; 16(7): 896-913.
23. Ellor SV, Pagano-Young TA, Avgeropoulos NG. Glioblastoma: background, standard treatment paradigms, and supportive care considerations. J Law Med Ethics. 2014; 42(2): 171-82.
24. Stummer W, Pichlmeier U, Meinel T et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006; 7(5): 392-401.
25. Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med. 2005; 352(10): 987-96.
26. Stupp R, Taillibert S, Kanner A et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017; 318(23): 2306-16.
27. Ameratunga M, Pavlakis N, Wheeler H et al. Anti-angiogenic therapy for high-grade glioma. Cochrane Database Syst Rev. 2018; 11(11): CD008218- CD008218.
28. Stevens GH. Antiepileptic therapy in patients with central nervous system malignancies. Curr Neurol Neurosci Rep. 2006; 6(4): 311-8.
29. Shao M, Liu W, Wang Y. Differentially expressed LncRNAs as potential prognostic biomarkers for glioblastoma. Cancer Genetics. 2018; 226-7: 23-9.
30. Chen HH, Zong J, Wang SJ. LncRNA GAPLINC promotes the growth and metastasis of glioblastoma by sponging miR-331-3p. Eur Rev Med Pharmacol Sci. 2019; 23(1): 262-70.
31. Li J, Ji X, Wang H. Targeting Long Noncoding RNA HMMR-AS1 Suppresses and Radiosensitizes Glioblastoma. Neoplasia. 2018; 20(5): 456-66.
32. Li Q, Dong C, Cui J et al. Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme. J Exp Clin Cancer Res. 2018; 37(1): 265.
33. Tang G, Luo L, Zhang J et al. lncRNA LINC01057 promotes mesenchymal differentiation by activating NF-κB signaling in glioblastoma. Cancer Letters. 2021; 498: 152-64.
34. Baspinar Y, Elmaci I, Ozpinar A et al. Long non-coding RNA MALAT1 as a key target in pathogenesis of glioblastoma. Janus faces or Achilles’ heal? Gene. 2020; 739: 144518.
35. Liao K, Lin Y, Gao W et al. Blocking lncRNA MALAT1/miR-199a/ZHX1 Axis Inhibits Glioblastoma Proliferation and Progression. Molecular Therapy – Nucleic Acids. 2019; 18: 388-99.
36. Li Z, Zhang J, Zheng H et al. Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib, overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme. J Exp Clin Cancer Res. 2019; 38(1): 380.
37. Ren J, Yang Y, Xue J et al. Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095. Biochem Biophys Res Commun. 2018; 496(2): 712-8.
38. Mazor G, Levin L, Picard D et al. The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells. Cell Death Dis. 2019; 10(3): 246.
39. Andrews LP, Yano H, Vignali DAA. Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups. Nat Immunol. 2019; 20(11): 1425-34.
40. Sabahi M, Jabbari P, Alizadeh Haghighi M et al. Proposing a tandem AND-gate CAR T cell targeting glioblastoma multiforme. Med Hypotheses. 2020; 137: 109559.
41. Aguilar B, Sarkissian A, Brito A et al. 275. Optimization of IL13Rα2-Specific CAR T Cells for Clinical Development Using Orthotopic Human Glioblastoma Models in NSG Mice. Mol Ther. 2016; 24: S109.
42. Keskin DB, Anandappa AJ, Sun J et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019; 565(7738): 234-9.
43. Burger MC, Zhang C, Harter PN et al. CAR-Engineered NK Cells for the Treatment of Glioblastoma: Turning Innate Effectors Into Precision Tools for Cancer Immunotherapy. Front Immunol. 2019; 10: 2683.
44. Peereboom D, Nabors LB, Kumthekar P et al. 373O – Results of phase II trial of SL-701, a novel immunotherapy targeting IL-13Ra2, EphA2, and survivin, in adults with second-line recurrent glioblastoma (GBM). Ann Oncol. 2018; 29: viii122-viii123.
45. Gardell JL, Matsumoto LR, Chinn H et al. Human macrophages engineered to secrete a bispecific T cell engager support antigen-dependent T cell responses to glioblastoma. J Immunother Cancer. 2020; 8(2): e001202.
46. Cui J, Wang H, Medina R et al. Inhibition of PP2A with LB-100 Enhances Efficacy of CAR-T Cell Therapy Against Glioblastoma. Cancers (Basel). 2020; 12(1):139.
47. Do AS-MS, Amano T, Edwards LA et al. CD133 mRNA-Loaded Dendritic Cell Vaccination Abrogates Glioma Stem Cell Propagation in Humanized Glioblastoma Mouse Model. Mol Ther – Oncolytics. 2020; 18: 295-303.
48. Jin L, Ge H, Long Y et al. CD70, a novel target of CAR T-cell therapy for gliomas. Neuro Oncol. 2018; 20(1): 55-65.
49. Pellegatta S, Savoldo B, Su C et al. 507. Chondroitin Sulfate Proteoglycan 4 (CSPG4)-Redirected T Cells Eliminate Glioblastoma-Derived Neurospheres. Mol Ther. 2016; 24: S202.
50. Jung IY, Kim YY , Yu HS et al. CRISPR/Cas9-Mediated Knockout of DGK Improves Antitumor Activities of Human T Cells. Cancer Res. 2018; 78(16): 4692-703.
51. O'Rourke DM, Nasrallah MP, Desai A et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017; 9(399): eaaa0984
52. Nakazawa T, Natsume A, Nishimura F et al. Effect of CRISPR/Cas9-Mediated PD-1-Disrupted Primary Human Third-Generation CAR-T Cells Targeting EGFRvIII on In Vitro Human Glioblastoma Cell Growth. Cells. 2020; 9(4): 998.
53. Choi BD, Yu X, Castano AP et al. CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma. J Immunother Cancer. 2019; 7(1): 304.
54. Liuzzi AR, Agliardi G, Becher B et al. 106P – A Single Dose of Local IL-12 Promotes Anti-Tumor Effect of Anti-EGFRvIII-CAR-T Cells in a Syngeneic Murine Model of Glioblastoma. Ann Oncol. 2019; 30: xi40.
55. Song Y, Liu Q, Zuo T et al. Combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model. Cell Immunol. 2020; 352: 104112.
56. Ahmed N, Brawley V, Hegde M et al. HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2017; 3(8): 1094-101.
57. Sanber K, Nawas Z, Salsman V et al. Modulation of inhibitory receptor signaling pathways improves CAR T cell activity against glioblastoma. Cytotherapy. 2020; 22(5 suppl): S19-S20.
58. Brown CE, Alizadeh D, Starr R et al. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016; 375(26): 2561-9.
59. Kim GB, Aragon-Sanabria V, Randolph L et al. High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma. Bioact Mater. 2020; 5(3): 624-35.
60. Møller HG, Rasmussen AP, Andersen HH et al. A Systematic Review of MicroRNA in Glioblastoma Multiforme: Micro-modulators in the Mesenchymal Mode of Migration and Invasion. Mol Neurobiol. 2013; 47(1): 131-44.
61. Marino A, Almici E, Migliorin S et al. Piezoelectric barium titanate nanostimulators for the treatment of glioblastoma multiforme. J Colloid Interface Sci. 2019; 538: 449-61.
62. Li T-F, Li K, Zhang Q et al. Dendritic cell-mediated delivery of doxorubicin-polyglycerol-nanodiamond composites elicits enhanced anti-cancer immune response in glioblastoma. Biomaterials. 2018; 181: 35-52.
63. Banerjee I, De K, Mukherjee D et al. Paclitaxel-loaded solid lipid nanoparticles modified with Tyr-3-octreotide for enhanced anti-angiogenic and antiglioma therapy. Acta Biomater. 2016; 38: 69-81.
64. Wu S-Q, Yang C-X, Yan X-P. A Dual-Functional Persistently Luminescent Nanocomposite Enables Engineering of Mesenchymal Stem Cells for Homing and Gene Therapy of Glioblastoma. Adv Funct Mater. 2017; 27(11): 1604992.
65. Roth P, Mason WP, Richardson PG et al. Proteasome inhibition for the treatment of glioblastoma. Expert Opin Investig Drugs. 2020; 29(10): 1133-41.
66. Rahman MA, Gras Navarro A, Brekke J et al. Bortezomib administered prior to temozolomide depletes MGMT, chemosensitizes glioblastoma with unmethylated MGMT promoter and prolongs animal survival. Br J Cancer. 2019; 121(7): 545-55.
67. Cloughesy TF, Mochizuki AY, Orpilla JR et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019; 25(3): 477-86.
68. Guetta-Terrier C, Akosmam B, Chen JS et al. 185 Poster – Antibody blockade resets Chi3L1-induced glioma stem cell phenotypic transitions and reduces glioblastoma tumor burden. Eur J Cancer. 2020; 138: S52.
69. Westphal M, Heese O, Steinbach JP et al. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer. 2015; 51(4): 522-32.
70. Harris-Bookman S, Mathios D, Martin AM et al. Expression of LAG-3 and efficacy of combination treatment with anti-LAG-3 and anti-PD-1 monoclonal antibodies in glioblastoma. Int J Cancer. 2018; 143(12): 3201-8.
71. Arnold AE, Malek-Adamian E, Le PU et al. Antibody-Antisense Oligonucleotide Conjugate Downregulates a Key Gene in Glioblastoma Stem Cells. Mol Ther Nucleic Acids. 2018; 11: 518-27.
72. Lu X, Wang M, Qiang J et al. Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR 379–5p/MAP3K2 axis. Eur J Pharmacol. 2019; 863: 172643.
73. Memari E, Maghsoudi A, Yazdian F et al. Synthesis of PHB-co-PEI nanoparticles as gene carriers for miR-128-encoding plasmid delivery to U87 glioblastoma cells. Colloids Surf A: Physicochem Eng Asp. 2020; 599: 124898.
74. Singh A, Srivastava N, Yadav A et al. Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma. Neoplasia. 2020; 22(10): 497-510.
75. Pan C-M, Chan K-H, Chen C-H et al. MicroRNA-7 targets T-Box 2 to inhibit epithelial-mesenchymal transition and invasiveness in glioblastoma multiforme. Cancer Lett. 2020; 493: 133-42.
76. Rezaei T, Hejazi M, Mansoori B et al. microRNA-181a mediates the chemo-sensitivity of glioblastoma to carmustine and regulates cell proliferation, migration, and apoptosis. Eur J Pharmacol. 2020; 888: 173483.
77. Zhang Y-X, Li X-F, Yuan G-Q et al. β-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G2/M phase transition. J Biol Chem. 2017; 292(21): 8933-47.
78. Wang S, Fan Y, Xu Y et al. GDNFOS1 knockdown decreases the invasion and viability of glioblastoma cells. Exp Ther Med. 2019; 18(2): 1315-22.
79. Lu YJ, Lan YH, Chuang CC et al. Injectable Thermo-Sensitive Chitosan Hydrogel Containing CPT-11-Loaded EGFR-Targeted Graphene Oxide and SLP2
shRNA for Localized Drug/Gene Delivery in Glioblastoma Therapy. Int J Mol Sci. 2020; 21(19): 7111.
80. Lee JA, Ayat N, Sun Z et al. Improving Radiation Response in Glioblastoma Using ECO Nanoparticle Delivery of siRNA Targeting DNA Damage Repair. Int J Radiat Oncol Biol Phys. 2017; 99(2 Suppl): E604.
81. Azambuja JH, Schuh RS, Michels LR et al. Blockade of CD73 delays glioblastoma growth by modulating the immune environment. Cancer Immunol Immunother. 2020; 69(9): 1801-12.
82. Danhier F, Messaoudi K, Lemaire L et al. Combined anti-Galectin-1 and anti-EGFR siRNA-loaded chitosan-lipid nanocapsules decrease temozolomide resistance in glioblastoma: In vivo evaluation. Int J Pharm. 2015; 481(1): 154-61.
83. Ding X, Deng G, Liu J et al. GOLM1 silencing inhibits the proliferation and motility of human glioblastoma cells via the Wnt/β-catenin signaling pathway. Brain Res. 2019; 1717: 117-26.
84. Önay Uçar E, Şengelen A. Resveratrol and siRNA in combination reduces Hsp27 expression and induces caspase-3 activity in human glioblastoma cells. Cell Stress Chaperones. 2019; 24(4): 763-75.
85. Wei J, Marisetty A, Schrand B et al. Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target. J Clin Invest. 2019; 129(1): 137-49.
86. Zheng M, Liu Y, Wang Y et al. ROS-Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy. Adv Mater. 2019; 31(37): e1903277.
87. Cen B, Wei Y, Huang W et al. An Efficient Bivalent Cyclic RGD-PIK3CB siRNA Conjugate for Specific Targeted Therapy against Glioblastoma In Vitro and In Vivo. Mol Ther Nucleic Acids. 2018; 13: 220-32.
88. Esposito CL, Nuzzo S, Catuogno S et al. STAT3 Gene Silencing by Aptamer-siRNA Chimera as Selective Therapeutic for Glioblastoma. Mol Ther Nucleic Acids. 2018; 10: 398-411.
89. Wu S, Luo C, Hameed NUF et al. UCP2 silencing in glioblastoma reduces cell proliferation and invasiveness by inhibiting p38 MAPK pathway. Exp Cell Res. 2020; 394(1): 112110.
90. Yang J, Zhang Q, Liu Y et al. Nanoparticle-based co-delivery of siRNA and paclitaxel for dual-targeting of glioblastoma. Nanomedicine (Lond). 2020; 15(14): 1391-409.
91. Rosenthal M, Clement PM, Campone M et al. Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. ESMO Open. 2020; 5(4): e000672.
92. Das A, Cheng RR, Hilbert ML et al. Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG ROS1 Fusion-Positive Glioblastoma. Cancer Growth Metastasis. 2015; 8: 51-60.
93. Zhu Y-G, Lv Y-X, Guo C-Y et al. Harmine inhibits the proliferation and migration of glioblastoma cells via the FAK/AKT pathway. Life Sci. 2021; 270: 119112.
94. Weller J, Tzaridis T, Mack F et al. Health-related quality of life and neurocognitive functioning with lomustine temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2019; 20(10): 1444-53.
95. Zielke S, Meyer N, Mari M et al. Loperamide, pimozide, and STF-62247 trigger autophagy-dependent cell death in glioblastoma cells. Cell Death Dis. 2018; 9(10): 994.
96. da Fonseca CO, Simão M, Lins IR et al. Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma. J Cancer Res Clin Oncol. 2011; 137(2): 287-93.
97. Sachdeva R, Wu M, Smiljanic S et al. ID1 Is Critical for Tumorigenesis and Regulates Chemoresistance in Glioblastoma. Cancer Res. 2019; 79(16): 4057-71.
98. Biau J, Thivat E, Chautard E et al. Phase 1 trial of ralimetinib (LY 2228820) with radiotherapy plus concomitant temozolomide in the treatment of newly diagnosed glioblastoma. Radiother Oncol. 2021; 154: 227-34.
99. Detti B, Scoccianti S, Lucidi S et al. Regorafenib in glioblastoma recurrence: A case report. Cancer Treat Res Commun. 2021; 26: 100263.