The Molecular Landscape of Glioblastoma: Implications for Diagnosis and Therapy

Year 2024, Volume: 83 Issue: 2, 232 - 246, 19.12.2024

Özlem Yıldırım , Evren Onay-ucar

https://doi.org/10.26650/EurJBiol.2024.1508396

Abstract

Glioblastoma, classified as grade IV astrocytoma by the World Health Organisation, is the most common and malignant primary brain tumour in adults, with a high mortality rate. It accounts for 14.5% of central nervous system tumours and 45.6% of primary malignant brain tumours, with an annual incidence of 3.19 per 100,000 people. Despite advances in our understanding of its molecular biology, patient outcomes remain poor, with a median survival of approximately 1 year. Glioblastoma is categorised into four subtypes: IDH wild-type, IDH mutant, not otherwise specified (NOS), and not elsewhere classified (NEC), each affecting prognosis and treatment. Key molecular alterations include IDH1/2, ATRX, TERT, TP53, B-RAF, EGFR, MGMT, and PTEN mutations, which contribute to tumour behaviour and therapeutic targets. Current diagnostic methods, including magnetic resonance imaging and advanced molecular imaging, aid in accurate diagnosis and treatment planning. Although existing therapies offer limited survival benefits, novel treatments like immunotherapy, oncolytic viral therapy, and targeted molecular therapies, are currently being investigated. These emerging therapies overcome challenges such as the blood-brain barrier and tumour heterogeneity, providing hope for improved outcomes. Future perspectives emphasise the importance of integrating molecular biomarkers, optimising treatment strategies, and enhancing clinical trial designs to develop more effective therapies for patients with glioblastoma.This review aims to delve into the intricate facets of glioblastoma, including its classification, histopathology, interactions with the microenvironment, molecular pathogenesis, diagnostic imaging techniques, clinical progression, current therapeutic approaches, challenges in treatment, identifiable risk factors, and exploration of emerging therapies and prospects in glioblastoma management.

Keywords

Glioblastoma, Temozolomide, IDH mutations, Diagnostic imaging, Blood-brain barrier

References

• Koshy M, Villano JL, Dolecek TA, et al. Improved survival time trends for glioblastoma using the SEER 17 population-based reg-istries. JNeurooncol. 2012;107:207-212. google scholar
• Koshy M, Villano JL, Dolecek TA, et al. Improved survival time trends for glioblastoma using the SEER 17 population-based reg-istries. JNeurooncol. 2012;107:207-212. google scholar
• Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: Primary brain and central nervous system tumors di-agnosed in the United States in 2006-2010. Neuro-Oncology. 2013;15-ii56. google scholar
• Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: Primary brain and central nervous system tumors di-agnosed in the United States in 2006-2010. Neuro-Oncology. 2013;15-ii56. google scholar
• Batash R, Asna N, Schaffer P, et al. Glioblastoma multiforme, di-agnosis and treatment; Recent literature review. Curr Med Chem. 2017;24:3002-3009. google scholar
• Batash R, Asna N, Schaffer P, et al. Glioblastoma multiforme, di-agnosis and treatment; Recent literature review. Curr Med Chem. 2017;24:3002-3009. google scholar
• Ostrom QT, Bauchet L, Davis FG, et al. The epidemiology of glioma in adults: A “state of the science” review. Neuro Oncol. 2014;16:896-913. google scholar
• Ostrom QT, Bauchet L, Davis FG, et al. The epidemiology of glioma in adults: A “state of the science” review. Neuro Oncol. 2014;16:896-913. google scholar
• Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous sys-tem: A summary. Acta Neuropathol. 2016;131:803-820. google scholar
• Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous sys-tem: A summary. Acta Neuropathol. 2016;131:803-820. google scholar
• Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-773. google scholar
• Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-773. google scholar
• Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013;19:764-772. google scholar
• Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013;19:764-772. google scholar
• Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(1):97-109. google scholar
• Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(1):97-109. google scholar
• Capper D, Zentgraf H, Balss J, et al. Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol. 2009; 118(1):599-601. google scholar
• Capper D, Zentgraf H, Balss J, et al. Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol. 2009; 118(1):599-601. google scholar
• Brat DJ, Aldape K, Colman H, et al. cIMPACT-NOW update 3: Recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. Acta Neuropathol. 2018;136(5):805-810. google scholar
• Brat DJ, Aldape K, Colman H, et al. cIMPACT-NOW update 3: Recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. Acta Neuropathol. 2018;136(5):805-810. google scholar
• Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555(7697):469-474. google scholar
• Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555(7697):469-474. google scholar
• Ferrer VP, Moura Neto V, Mentlein R. Glioma infiltration and extracellular matrix: Key players and modulators. Glia. 2018;66:1542-1565. google scholar
• Ferrer VP, Moura Neto V, Mentlein R. Glioma infiltration and extracellular matrix: Key players and modulators. Glia. 2018;66:1542-1565. google scholar
• Chen JT, Mao SF, Li HF, et al. The pathological structure of the perivascular niche in different microvascular patterns of glioblastoma. PLoS One. 2017;12(8):12. doi: 10.1371/jour-nal.pone.018283. google scholar
• Chen JT, Mao SF, Li HF, et al. The pathological structure of the perivascular niche in different microvascular patterns of glioblastoma. PLoS One. 2017;12(8):12. doi: 10.1371/jour-nal.pone.018283. google scholar
• Zhao X, Chen RJ, Liu M, Feng JF, Chen J, Hu KL. Remodeling the blood-brain barrier microenvironment by natural products for brain tumor therapy. Acta Pharm Sin B. 2017;7(5):541-553. google scholar
• Zhao X, Chen RJ, Liu M, Feng JF, Chen J, Hu KL. Remodeling the blood-brain barrier microenvironment by natural products for brain tumor therapy. Acta Pharm Sin B. 2017;7(5):541-553. google scholar
• Nakod PS, Kim Y, Rao SS. Biomimetic models to exam-ine microenvironmental regulation of glioblastoma stem cells. Cancer Lett. 2018;429:41-53. google scholar
• Nakod PS, Kim Y, Rao SS. Biomimetic models to exam-ine microenvironmental regulation of glioblastoma stem cells. Cancer Lett. 2018;429:41-53. google scholar
• Dey M, Ulasov IV, Lesniak MS. Virotherapy against malignant glioma stem cells. Cancer Lett. 2010;289(1):1-10. google scholar
• Dey M, Ulasov IV, Lesniak MS. Virotherapy against malignant glioma stem cells. Cancer Lett. 2010;289(1):1-10. google scholar
• Simon T, Gagliano T, Giamas G. Direct effects of anti-angiogenic therapies on tumor cells: VEGF signaling. Trends Mol Med. 2017;23(3):282-292. google scholar
• Simon T, Gagliano T, Giamas G. Direct effects of anti-angiogenic therapies on tumor cells: VEGF signaling. Trends Mol Med. 2017;23(3):282-292. google scholar
• Fessler E, Borovski T, Medema JP. Endothelial cells induce cancer stem cell features in differentiated glioblastoma cells via bFGF. Mol Cancer. 2015;14:157. google scholar
• Fessler E, Borovski T, Medema JP. Endothelial cells induce cancer stem cell features in differentiated glioblastoma cells via bFGF. Mol Cancer. 2015;14:157. google scholar
• Hu F, Ku MC, Markovic D, et al. Glioma associated microglial MMP9 expression is upregulated by TLR2 signalling and sensi-tive to minocycline. Int J Cancer. 2014;135(11):2569-2578. google scholar
• Hu F, Ku MC, Markovic D, et al. Glioma associated microglial MMP9 expression is upregulated by TLR2 signalling and sensi-tive to minocycline. Int J Cancer. 2014;135(11):2569-2578. google scholar
• Jakel S, Dimou L. Glial cells and their function in the adult brain: A journey through the history of their ablation. Front Cell Neurosci. 2017;11. doi: 10.3339/fncel.2017.00024 google scholar
• Jakel S, Dimou L. Glial cells and their function in the adult brain: A journey through the history of their ablation. Front Cell Neurosci. 2017;11. doi: 10.3339/fncel.2017.00024 google scholar
• Quail DF, Joyce JA. The microenvironmental landscape of brain tumors. Cancer Cell. 2017;31(3):326-341. google scholar
• Quail DF, Joyce JA. The microenvironmental landscape of brain tumors. Cancer Cell. 2017;31(3):326-341. google scholar
• Phillips HS, Kharbanda S, Chen R, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006;9(1):157-173. google scholar
• Phillips HS, Kharbanda S, Chen R, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006;9(1):157-173. google scholar
• 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. google scholar
• 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. google scholar
• Sturm D, Witt H, Hovestadt V, et al. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell. 2012;22(1):425-437. google scholar
• Sturm D, Witt H, Hovestadt V, et al. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell. 2012;22(1):425-437. google scholar
• Parsons DW, Jones S, Zhang X, et al. An integrated ge-nomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807-1812. google scholar
• Parsons DW, Jones S, Zhang X, et al. An integrated ge-nomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807-1812. google scholar
• Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is suffi-cient to establish the glioma hypermethylator phenotype. Nature. 2012;483(1):479-483. google scholar
• Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is suffi-cient to establish the glioma hypermethylator phenotype. Nature. 2012;483(1):479-483. google scholar
• Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17(1):510-522. google scholar
• Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17(1):510-522. google scholar
• Horbinski C. What do we know about IDH1/2 mutations so far, and how do we use it? Acta Neuropathol. 2013;125(5):621-636. google scholar
• Horbinski C. What do we know about IDH1/2 mutations so far, and how do we use it? Acta Neuropathol. 2013;125(5):621-636. google scholar
• Capper D, Weissert S, Balss J, et al. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol. 2010;20(1):245-254. google scholar
• Capper D, Weissert S, Balss J, et al. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol. 2010;20(1):245-254. google scholar
• DeWitt JC, Jordan JT, Frosch MP, et al. Cost-effectiveness of IDH testing in diffuse gliomas according to the 2016 WHO classifica-tion of tumors of the central nervous system recommendations. Neuro Oncol. 2017;19(12):1640-1650. google scholar
• DeWitt JC, Jordan JT, Frosch MP, et al. Cost-effectiveness of IDH testing in diffuse gliomas according to the 2016 WHO classifica-tion of tumors of the central nervous system recommendations. Neuro Oncol. 2017;19(12):1640-1650. google scholar
• Labussiere M, Di Stefano AL, Gleize V, et al. TERT promoter mutations in gliomas, genetic associations and clinicopathological correlations. BrJ Cancer. 2014;111(1):2024-2032. google scholar
• Labussiere M, Di Stefano AL, Gleize V, et al. TERT promoter mutations in gliomas, genetic associations and clinicopathological correlations. BrJ Cancer. 2014;111(1):2024-2032. google scholar
• Schwartzentruber J, Korshunov A, Liu XY, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482:226-231. google scholar
• Schwartzentruber J, Korshunov A, Liu XY, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482:226-231. google scholar
• Chaurasia A, Park SH, Seo JW, et al. Immunohistochemical analy-sis of ATRX, IDH1 and p53 in glioblastoma and their correlations with patient survival. J Korean Med Sci. 2016;31:1208-1214. google scholar
• Chaurasia A, Park SH, Seo JW, et al. Immunohistochemical analy-sis of ATRX, IDH1 and p53 in glioblastoma and their correlations with patient survival. J Korean Med Sci. 2016;31:1208-1214. google scholar
• Killela PJ, Reitman ZJ, Jiao Y, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA. 2013;110(1):6021-6026. google scholar
• Killela PJ, Reitman ZJ, Jiao Y, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA. 2013;110(1):6021-6026. google scholar
• Vinagre J, Pinto V, Celestino R, et al. Telomerase promoter mu-tations in cancer: An emerging molecular biomarker? Virchows Arch. 2014;465:119-133. google scholar
• Vinagre J, Pinto V, Celestino R, et al. Telomerase promoter mu-tations in cancer: An emerging molecular biomarker? Virchows Arch. 2014;465:119-133. google scholar
• Nakahara Y, Okamoto H, Mineta T, et al. Expression of the Wilms’ tumor gene product WT1 in glioblastomas and medulloblastomas. Brain Tumor Pathol. 2004;21:113-116. google scholar
• Nakahara Y, Okamoto H, Mineta T, et al. Expression of the Wilms’ tumor gene product WT1 in glioblastomas and medulloblastomas. Brain Tumor Pathol. 2004;21:113-116. google scholar
• Fredriksson NJ, Ny L, Nilsson JA, et al. Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types. Nat Genet. 2014;46:1258-1263. google scholar
• Fredriksson NJ, Ny L, Nilsson JA, et al. Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types. Nat Genet. 2014;46:1258-1263. google scholar
• Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372:2499-2508. google scholar
• Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372:2499-2508. google scholar
• Spiegl-Kreinecker S, Lötsch D, Ghanim B, et al. Prognostic qual-ity of activating TERT promoter mutations in glioblastoma: In-teraction with the rs2853669 polymorphism and patient age at diagnosis. Neuro-Oncology. 2015;17:1231-1240. google scholar
• Spiegl-Kreinecker S, Lötsch D, Ghanim B, et al. Prognostic qual-ity of activating TERT promoter mutations in glioblastoma: In-teraction with the rs2853669 polymorphism and patient age at diagnosis. Neuro-Oncology. 2015;17:1231-1240. google scholar
• Olympios N, Gilard V, Marguet F, et al. TERT promoter alterations in glioblastoma: A systematic review. Cancers. 2021;13:1147. google scholar
• Olympios N, Gilard V, Marguet F, et al. TERT promoter alterations in glioblastoma: A systematic review. Cancers. 2021;13:1147. google scholar
• Wang TJ, Huang MS, Hong CY, et al. Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblas-toma tumorigenicity in situ. Biochem Biophys Res Commun. 2001;287:173-180. google scholar
• Wang TJ, Huang MS, Hong CY, et al. Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblas-toma tumorigenicity in situ. Biochem Biophys Res Commun. 2001;287:173-180. google scholar
• Oren M, Rotter V. Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol. 2010;2(2):a001107. doi: 10.1101/csh-perspect.a001107 google scholar
• Oren M, Rotter V. Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol. 2010;2(2):a001107. doi: 10.1101/csh-perspect.a001107 google scholar
• Adorno M, Cordenonsi M, Montagner M, et al. A Mutant-p53/Smad Complex Opposes p63 to Empower TGF^-Induced Metastasis. Cell. 2009;137:87-98. google scholar
• Adorno M, Cordenonsi M, Montagner M, et al. A Mutant-p53/Smad Complex Opposes p63 to Empower TGF^-Induced Metastasis. Cell. 2009;137:87-98. google scholar
• Behling F, Barrantes-Freer A, Skardelly M, et al. Frequency of BRAF V600E mutations in 969 central nervous system neoplasms. Diagn Pathol. 2016;11:55. doi: 10.1186/s13000-016-0506-2. google scholar
• Behling F, Barrantes-Freer A, Skardelly M, et al. Frequency of BRAF V600E mutations in 969 central nervous system neoplasms. Diagn Pathol. 2016;11:55. doi: 10.1186/s13000-016-0506-2. google scholar
• Bautista F, Paci A, Minard-Colin V, et al. Vemurafenib in pediatric patients with BRAFV 600E mutated high-grade gliomas. Pediatr Blood Cancer. 2014;61(1):1101-1103. google scholar
• Bautista F, Paci A, Minard-Colin V, et al. Vemurafenib in pediatric patients with BRAFV 600E mutated high-grade gliomas. Pediatr Blood Cancer. 2014;61(1):1101-1103. google scholar
• Patel R, Leung HY. Targeting the EGFR-family for therapy: Biological challenges and clinical perspective. Curr Pharm Des. 2012;18:2672-2679. google scholar
• Patel R, Leung HY. Targeting the EGFR-family for therapy: Biological challenges and clinical perspective. Curr Pharm Des. 2012;18:2672-2679. google scholar
• Ekstrand AJ, Sugawa N, James CD, Collins VP. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci USA. 1992;89(1):4309-4313. google scholar
• Ekstrand AJ, Sugawa N, James CD, Collins VP. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci USA. 1992;89(1):4309-4313. google scholar
• Cowppli-Bony A, Bouvier G, Rue M, et al. Brain tumors and hor-monal factors: Review of the epidemiological literature. Cancer Causes Control. 2011;22:697-714. google scholar
• Cowppli-Bony A, Bouvier G, Rue M, et al. Brain tumors and hor-monal factors: Review of the epidemiological literature. Cancer Causes Control. 2011;22:697-714. google scholar
• Smith JS, Tachibana I, Passe SM, et al. PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst. 2001;93:1246-1256. google scholar
• Smith JS, Tachibana I, Passe SM, et al. PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst. 2001;93:1246-1256. google scholar
• Heimberger AB, Sampson JH. The PEPvIII-KLH (CDX-110) vac-cine in glioblastoma multiforme patients. Expert Opin Biol Ther. 2009;9:1087-1098. google scholar
• Heimberger AB, Sampson JH. The PEPvIII-KLH (CDX-110) vac-cine in glioblastoma multiforme patients. Expert Opin Biol Ther. 2009;9:1087-1098. google scholar
• Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003. google scholar
• Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003. google scholar
• Malmström A, Gr0nberg BH, Marosi C, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated ra-diotherapy in patients older than 60 years with glioblastoma: The Nordic randomised, phase 3 trial. Lancet Oncol. 2012;13(1):916-926. google scholar
• Malmström A, Gr0nberg BH, Marosi C, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated ra-diotherapy in patients older than 60 years with glioblastoma: The Nordic randomised, phase 3 trial. Lancet Oncol. 2012;13(1):916-926. google scholar
• Weller M, van den Bent M, Hopkins K, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblas-toma. Lancet Oncol. 2014;15(9):e395-403. doi: 10.1016/S1470-2045(14)70011-7 google scholar
• Weller M, van den Bent M, Hopkins K, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblas-toma. Lancet Oncol. 2014;15(9):e395-403. doi: 10.1016/S1470-2045(14)70011-7 google scholar
• Hopkins BD, Hodakoski C, Barrows D, Mense SM, Parsons RE. PTEN function: The long and the short of it. Trends Biochem Sci. 2014;39:183-190. google scholar
• Hopkins BD, Hodakoski C, Barrows D, Mense SM, Parsons RE. PTEN function: The long and the short of it. Trends Biochem Sci. 2014;39:183-190. google scholar
• Koul D. PTEN signaling pathways in glioblastoma. Cancer Biol Ther. 2008;7:1321-1325. google scholar
• Koul D. PTEN signaling pathways in glioblastoma. Cancer Biol Ther. 2008;7:1321-1325. google scholar
• Knobbe CB, Merlo A, Reifenberger G. PTEN signalling in gliomas. Neuro-Oncology. 2002;4:196-210. google scholar
• Knobbe CB, Merlo A, Reifenberger G. PTEN signalling in gliomas. Neuro-Oncology. 2002;4:196-210. google scholar
• La Fougere C, Suchorska B, Bartenstein P, et al. Molecular imag-ing of gliomas with PET: Opportunities and limitations. Neuro Oncol. 2011;13(1):806-819. google scholar
• La Fougere C, Suchorska B, Bartenstein P, et al. Molecular imag-ing of gliomas with PET: Opportunities and limitations. Neuro Oncol. 2011;13(1):806-819. google scholar
• Kono K, Inoue Y, Nakayama K, et al. The role of diffusion-weighted imaging in patients with brain tumors. AJNR Am J Neuroradiol. 2001;22(1):1081-1088. google scholar
• Kono K, Inoue Y, Nakayama K, et al. The role of diffusion-weighted imaging in patients with brain tumors. AJNR Am J Neuroradiol. 2001;22(1):1081-1088. google scholar
• Law M, Yang S, Wang H, et al. Glioma grading: Sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol. 2003;24(1):1989-1998. google scholar
• Law M, Yang S, Wang H, et al. Glioma grading: Sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol. 2003;24(1):1989-1998. google scholar
• Roa W, Brasher PM, Bauman G, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multi-forme: A prospective randomized clinical trial. J Clin Oncol. 2004;22(1):1583-1588. google scholar
• Roa W, Brasher PM, Bauman G, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multi-forme: A prospective randomized clinical trial. J Clin Oncol. 2004;22(1):1583-1588. google scholar
• Taphoorn MJ, Stupp R, Coens C, et al. Health-related quality of life in patients with glioblastoma: A randomised controlled trial. Lancet Oncol. 2005;6(1):937-944. google scholar
• Taphoorn MJ, Stupp R, Coens C, et al. Health-related quality of life in patients with glioblastoma: A randomised controlled trial. Lancet Oncol. 2005;6(1):937-944. google scholar
• Keime-Guibert F, Chinot O, Taillandier L, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007;356(1):1527-1535. google scholar
• Keime-Guibert F, Chinot O, Taillandier L, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007;356(1):1527-1535. google scholar
• Wick W, Menn O, Meisner C, et al. Pharmacotherapy of epileptic seizures in glioma patients: Who, when, why and how long? Onkologie. 2005;28(1):391-396. google scholar
• Wick W, Menn O, Meisner C, et al. Pharmacotherapy of epileptic seizures in glioma patients: Who, when, why and how long? Onkologie. 2005;28(1):391-396. google scholar
• Chaichana KL, Parker SL, Olivi A, et al. Long-term seizure out-comes in adult patients undergoing primary resection of malignant brain astrocytomas. J Neurosurg. 2009;111(1):282-292. google scholar
• Chaichana KL, Parker SL, Olivi A, et al. Long-term seizure out-comes in adult patients undergoing primary resection of malignant brain astrocytomas. J Neurosurg. 2009;111(1):282-292. google scholar
• Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(1):987-996. google scholar
• Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(1):987-996. google scholar
• Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolo-mide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J Clin Oncol. 2013;31(1):4085-4091. google scholar
• Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolo-mide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J Clin Oncol. 2013;31(1):4085-4091. google scholar
• Murphy ES, Xie H, Merchant TE, Yu JS, Chao ST, Suh JH. Re-view of cranial radiotherapy-induced vasculopathy. J Neurooncol. 2015;122(3):421-429. google scholar
• Murphy ES, Xie H, Merchant TE, Yu JS, Chao ST, Suh JH. Re-view of cranial radiotherapy-induced vasculopathy. J Neurooncol. 2015;122(3):421-429. google scholar
• Heffron TP. Challenges of developing small-molecule kinase in-hibitors for brain tumors and the need for emphasis on free drug levels. Neuro Oncol. 2018;20(3):307-312. google scholar
• Heffron TP. Challenges of developing small-molecule kinase in-hibitors for brain tumors and the need for emphasis on free drug levels. Neuro Oncol. 2018;20(3):307-312. google scholar
• Idbaih A, Canney M, Belin L, et al. Safety and feasibility of repeated and transient blood-brain barrier disruption by pulsed ultrasound in patients with recurrent glioblastoma. Clin Cancer Res. 2019;25(13):3793-3801. google scholar
• Idbaih A, Canney M, Belin L, et al. Safety and feasibility of repeated and transient blood-brain barrier disruption by pulsed ultrasound in patients with recurrent glioblastoma. Clin Cancer Res. 2019;25(13):3793-3801. google scholar
• Brennan CW, Verhaak RG, McKenna A, et al. TCGA Research Network. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462-477. google scholar
• Brennan CW, Verhaak RG, McKenna A, et al. TCGA Research Network. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462-477. google scholar
• Sottoriva A, Spiteri I, Piccirillo SG, et al. Intratumor heterogene-ity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA. 2013;110(10):4009-4014. google scholar
• Sottoriva A, Spiteri I, Piccirillo SG, et al. Intratumor heterogene-ity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA. 2013;110(10):4009-4014. google scholar
• Francis JM, Zhang CZ, Maire CL, et al. EGFR variant heterogene-ity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 2014;4(8):956-971. google scholar
• Francis JM, Zhang CZ, Maire CL, et al. EGFR variant heterogene-ity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 2014;4(8):956-971. google scholar
• Neftel C, Laffy J, Filbin MG, et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell. 2019;178(4):835-849. google scholar
• Neftel C, Laffy J, Filbin MG, et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell. 2019;178(4):835-849. google scholar
• Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344(6190):1396-1401. google scholar
• Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344(6190):1396-1401. google scholar
• Lan X, Jörg DJ, Cavalli FMG, et al. Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy. Nature. 2017;549(7671):227-232. google scholar
• Lan X, Jörg DJ, Cavalli FMG, et al. Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy. Nature. 2017;549(7671):227-232. google scholar
• Chen J, Li Y, Yu TS, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012;488(7412):522-526. google scholar
• Chen J, Li Y, Yu TS, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012;488(7412):522-526. google scholar
• Ohgaki H, Kim YH, Steinbach JP. Nervous system tumors as-sociated with familial tumor syndromes. Curr Opin Neurol. 2010;23(1):583-591. google scholar
• Ohgaki H, Kim YH, Steinbach JP. Nervous system tumors as-sociated with familial tumor syndromes. Curr Opin Neurol. 2010;23(1):583-591. google scholar
• Jonsson P, Lin AL, Young RJ, et al. Genomic correlates of disease progression and treatment response in prospectively characterized gliomas. Clin Cancer Res. 2019;25(18):5537-5547. google scholar
• Jonsson P, Lin AL, Young RJ, et al. Genomic correlates of disease progression and treatment response in prospectively characterized gliomas. Clin Cancer Res. 2019;25(18):5537-5547. google scholar
• Melin BS, Barnholtz-Sloan JS, Wrensch MR, et al. GliomaS-can Consortium. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibil-ity to glioblastoma and non-glioblastoma tumors. Nat Genet. 2017;49(5):789-794. google scholar
• Melin BS, Barnholtz-Sloan JS, Wrensch MR, et al. GliomaS-can Consortium. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibil-ity to glioblastoma and non-glioblastoma tumors. Nat Genet. 2017;49(5):789-794. google scholar
• Neglia JP, Robison LL, Stovall M, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006;98(1):1528-1537. google scholar
• Neglia JP, Robison LL, Stovall M, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006;98(1):1528-1537. google scholar
• Minniti G, Traish D, Ashley S, et al. Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: Update after an additional 10 years. J Clin Endocrinol Metab. 2005;90(1):800-804. google scholar
• Minniti G, Traish D, Ashley S, et al. Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: Update after an additional 10 years. J Clin Endocrinol Metab. 2005;90(1):800-804. google scholar
• Brada M, Ford D, Ashley S, et al. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. Br Med J. 1992;304(1):1343-1346. google scholar
• Brada M, Ford D, Ashley S, et al. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. Br Med J. 1992;304(1):1343-1346. google scholar
• Interphone Study Group. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Int J Epidemiol. 2010;39(1):675-694. google scholar
• Interphone Study Group. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Int J Epidemiol. 2010;39(1):675-694. google scholar
• Dziurzynski K, Chang SM, Heimberger AB, et al. Consensus on the role of human cytomegalovirus in glioblastoma. Neuro Oncol. 2012;14(1):246-255. google scholar
• Dziurzynski K, Chang SM, Heimberger AB, et al. Consensus on the role of human cytomegalovirus in glioblastoma. Neuro Oncol. 2012;14(1):246-255. google scholar
• Wick W, Platten M. CMV infection and glioma, a highly con-troversial concept struggling in the clinical arena. Neuro Oncol. 2014;16(1):332-333. google scholar
• Wick W, Platten M. CMV infection and glioma, a highly con-troversial concept struggling in the clinical arena. Neuro Oncol. 2014;16(1):332-333. google scholar
• Connelly JM, Malkin MG. Environmental risk factors for brain tumors. Curr Neurol Neurosci Rep. 2007;7(1):208-214. google scholar
• Connelly JM, Malkin MG. Environmental risk factors for brain tumors. Curr Neurol Neurosci Rep. 2007;7(1):208-214. google scholar
• Bondy ML, Scheurer ME, Malmer B, et al. Brain tumor epidemi-ology: Consensus from the Brain Tumor Epidemiology Consor-tium. Cancer. 2008;113(1):1953-1968. google scholar
• Bondy ML, Scheurer ME, Malmer B, et al. Brain tumor epidemi-ology: Consensus from the Brain Tumor Epidemiology Consor-tium. Cancer. 2008;113(1):1953-1968. google scholar
• Ostrom QT, Barnholtz-Sloan JS. Current state of our knowledge on brain tumor epidemiology. Curr Neurol Neurosci Rep. 2011;11(1):329-335. google scholar
• Ostrom QT, Barnholtz-Sloan JS. Current state of our knowledge on brain tumor epidemiology. Curr Neurol Neurosci Rep. 2011;11(1):329-335. google scholar
• Ohgaki H, Dessen P, Jourde B, et al. Genetic pathways to glioblastoma: A population-based study. Cancer Res. 2004;64:6892-6899. google scholar
• Ohgaki H, Dessen P, Jourde B, et al. Genetic pathways to glioblastoma: A population-based study. Cancer Res. 2004;64:6892-6899. google scholar
• Fukushima T, Favereaux A, Huang H, et al. Genetic alterations in primary glioblastomas in Japan. J Neuropathol Exp Neurol. 2006;65:12-18. google scholar
• Fukushima T, Favereaux A, Huang H, et al. Genetic alterations in primary glioblastomas in Japan. J Neuropathol Exp Neurol. 2006;65:12-18. google scholar
• UC Clinical Trials.http://www.ucclinicaltrials.com. Accessed on July 10, 2024. google scholar
• UC Clinical Trials.http://www.ucclinicaltrials.com. Accessed on July 10, 2024. google scholar
• Mayo Clinic. http://www.mayoclinic.org. Accessed on July 10, 2024. google scholar
• Mayo Clinic. http://www.mayoclinic.org. Accessed on July 10, 2024. google scholar
• Clinical Trials at UCSF. http://www.ucsfclinicaltrials.org. Ac-cessed on July 10, 2024. google scholar
• Clinical Trials at UCSF. http://www.ucsfclinicaltrials.org. Ac-cessed on July 10, 2024. google scholar
• Memorial Sloan Kettering Cancer Centre. http://www.mskcc.org. Accessed on July 10, 2024. google scholar
• Memorial Sloan Kettering Cancer Centre. http://www.mskcc.org. Accessed on July 10, 2024. google scholar
• Wilson CB. Current concepts in cancer: Brain tumors. N Engl J Med. 1979;300:1469-1471. google scholar
• Wilson CB. Current concepts in cancer: Brain tumors. N Engl J Med. 1979;300:1469-1471. google scholar
• Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of recurrent glioblastoma - Are we there yet? Neuro Oncol. 2013;15(1):4-27. google scholar
• Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of recurrent glioblastoma - Are we there yet? Neuro Oncol. 2013;15(1):4-27. google scholar
• Gramatzki D, Dehler S, Rushing EJ, et al. Glioblastoma in the canton of Zurich, Switzerland revisited, 2005 to 2009. Cancer. 2016;122(16):2206-2215. google scholar
• Gramatzki D, Dehler S, Rushing EJ, et al. Glioblastoma in the canton of Zurich, Switzerland revisited, 2005 to 2009. Cancer. 2016;122(16):2206-2215. google scholar
• Jackson CM, Kochel CM, Nirschl CJ, et al. Systemic tolerance mediated by melanoma brain tumors is reversible by radiotherapy and vaccination. Clin Cancer Res. 2016;22(5):1161-1172. google scholar
• Jackson CM, Kochel CM, Nirschl CJ, et al. Systemic tolerance mediated by melanoma brain tumors is reversible by radiotherapy and vaccination. Clin Cancer Res. 2016;22(5):1161-1172. google scholar
• Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16:275-287. google scholar
• Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16:275-287. google scholar
• Aurelian L. Oncolytic viruses as immunotherapy, progress and remaining challenges. OncoTargets Ther. 2016;9:2627-2637. google scholar
• Aurelian L. Oncolytic viruses as immunotherapy, progress and remaining challenges. OncoTargets Ther. 2016;9:2627-2637. google scholar
• Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480-489. google scholar
• Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480-489. google scholar
• Topalian SL, Drake CG, Pardoll DM. Immune checkpoint block-ade: A common denominator approach to cancer therapy. Cancer Cell. 2015;27:450-461. google scholar
• Topalian SL, Drake CG, Pardoll DM. Immune checkpoint block-ade: A common denominator approach to cancer therapy. Cancer Cell. 2015;27:450-461. google scholar
• 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):2561-2569. google scholar
• 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):2561-2569. google scholar
• 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 re-current glioblastoma. Sci Transl Med. 2017;9(399):eaaa0984 doi: 10.1126/scitranslmed.aaa0984 google scholar
• 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 re-current glioblastoma. Sci Transl Med. 2017;9(399):eaaa0984 doi: 10.1126/scitranslmed.aaa0984 google scholar
• Bagley SJ, Desai AS, Linette GP, June CH, O’Rourke DM. CAR T-cell therapy for glioblastoma: Recent clinical advances and future challenges. Neuro Oncol. 2018;20(11):1429-1438. google scholar
• Bagley SJ, Desai AS, Linette GP, June CH, O’Rourke DM. CAR T-cell therapy for glioblastoma: Recent clinical advances and future challenges. Neuro Oncol. 2018;20(11):1429-1438. google scholar
• Sadelain M, Riviere I, Riddell S. Therapeutic T cell engineering. Nature. 2017;545:423-431. google scholar
• Sadelain M, Riviere I, Riddell S. Therapeutic T cell engineering. Nature. 2017;545:423-431. google scholar
• Beyar-Katz O, Gill S. Advances in chimeric antigen receptor T cells. Curr Opin Hematol. 2020;27:368-377. google scholar
• Beyar-Katz O, Gill S. Advances in chimeric antigen receptor T cells. Curr Opin Hematol. 2020;27:368-377. google scholar
• Batlevi CL, Matsuki E, Brentjens RJ, Younes A. Novel im-munotherapies in lymphoid malignancies. Nat Rev Clin Onco. 2016;13:25-40. google scholar
• Batlevi CL, Matsuki E, Brentjens RJ, Younes A. Novel im-munotherapies in lymphoid malignancies. Nat Rev Clin Onco. 2016;13:25-40. google scholar
• Brown MP, Ebert LM, Gargett T. Clinical chimeric antigen receptor-T cell therapy: A new and promising treatment modal-ity for glioblastoma. Clin Transl Immunol. 2019;8(5):e1050. doi: 10.1002/cti2.1050 google scholar
• Brown MP, Ebert LM, Gargett T. Clinical chimeric antigen receptor-T cell therapy: A new and promising treatment modal-ity for glioblastoma. Clin Transl Immunol. 2019;8(5):e1050. doi: 10.1002/cti2.1050 google scholar
• Brown CE, Badie B, Barish ME, et al. Bioactivity and safety of IL13Ralpha2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res. 2015;21:4062-4072. google scholar
• Brown CE, Badie B, Barish ME, et al. Bioactivity and safety of IL13Ralpha2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res. 2015;21:4062-4072. google scholar
• 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;3:1094-1101. google scholar
• 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;3:1094-1101. google scholar
• Kaufmann JK, Chiocca EA. Glioma virus therapies between bench and bedside. Neuro Oncol. 2014;16(3):334-351. google scholar
• Kaufmann JK, Chiocca EA. Glioma virus therapies between bench and bedside. Neuro Oncol. 2014;16(3):334-351. google scholar
• Blitz SE, Kappel AD, Gessler FA, et al. Tumor-associated macrophages/microglia in glioblastoma oncolytic virotherapy: A double-edged sword. Int J Mol Sci. 2022;23(3):1808. doi: 10.3390/ijms23031808 google scholar
• Blitz SE, Kappel AD, Gessler FA, et al. Tumor-associated macrophages/microglia in glioblastoma oncolytic virotherapy: A double-edged sword. Int J Mol Sci. 2022;23(3):1808. doi: 10.3390/ijms23031808 google scholar
• Zhou C, Chen Q, Chen Y, Qin CF. Oncolytic Zika virus: New option for glioblastoma treatment. DNA Cell Biol. 2023;42:267-273. google scholar
• Zhou C, Chen Q, Chen Y, Qin CF. Oncolytic Zika virus: New option for glioblastoma treatment. DNA Cell Biol. 2023;42:267-273. google scholar
• Chen Q, Wu J, Ye Q, Ma F, Zhu Q, Wu Y, et al. Treatment of human glioblastoma with a live attenuated Zika virus vaccine can-didate. mBio. 2018;9(5):e01683-18. doi: 10.1128/mBio.01683-18 google scholar
• Chen Q, Wu J, Ye Q, Ma F, Zhu Q, Wu Y, et al. Treatment of human glioblastoma with a live attenuated Zika virus vaccine can-didate. mBio. 2018;9(5):e01683-18. doi: 10.1128/mBio.01683-18 google scholar
• Chiocca EA, Abbed KM, Tatter S, et al. A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther. 2004;10:958-966. google scholar
• Chiocca EA, Abbed KM, Tatter S, et al. A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther. 2004;10:958-966. google scholar
• Markert JM, Razdan SN, Kuo HC, et al. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther. 2014;22:1048-1055. google scholar
• Markert JM, Razdan SN, Kuo HC, et al. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther. 2014;22:1048-1055. google scholar
• Marelli G, Howells A, Lemoine NR, Wang Y. On-colytic viral therapy and the immune system: A double-edged sword against cancer. Front Immunol. 2018;9:866. doi: 10.3389/fimmu.2018.00866 google scholar
• Marelli G, Howells A, Lemoine NR, Wang Y. On-colytic viral therapy and the immune system: A double-edged sword against cancer. Front Immunol. 2018;9:866. doi: 10.3389/fimmu.2018.00866 google scholar
• Kicielinski KP, Chiocca EA, Yu JS, et al. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther. 2014;22:1056-1062. google scholar
• Kicielinski KP, Chiocca EA, Yu JS, et al. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther. 2014;22:1056-1062. google scholar
• Gujar S, Bell J, Diallo JS. SnapShot: Cancer immunother-apy with oncolytic viruses. Cell. 2019;176:1240-1240.e1. doi: 10.1016/j.cell.2019.01.051 google scholar
• Gujar S, Bell J, Diallo JS. SnapShot: Cancer immunother-apy with oncolytic viruses. Cell. 2019;176:1240-1240.e1. doi: 10.1016/j.cell.2019.01.051 google scholar
• Angom RS, Nakka NMR, Bhattacharya S. Advances in glioblas-toma therapy: An update on current approaches. Brain Sci. 2023;13:1536. doi: 10.3390/brainsci13111536 google scholar
• Angom RS, Nakka NMR, Bhattacharya S. Advances in glioblas-toma therapy: An update on current approaches. Brain Sci. 2023;13:1536. doi: 10.3390/brainsci13111536 google scholar
• Asija S, Chatterjee A, Yadav S, et al. Combinatorial approaches to effective therapy in glioblastoma (GBM): Current status and what the future holds. Int Rev Immunol. 2022;41:582-605. google scholar
• Asija S, Chatterjee A, Yadav S, et al. Combinatorial approaches to effective therapy in glioblastoma (GBM): Current status and what the future holds. Int Rev Immunol. 2022;41:582-605. google scholar
• Huang B, Li X, Li Y, Zhang J, Zong Z, Zhang H. Current immunotherapies for glioblastoma multiforme. Front Immunol. 2021;11:603911. doi: 10.3389/fimmu.2020.603911 google scholar
• Huang B, Li X, Li Y, Zhang J, Zong Z, Zhang H. Current immunotherapies for glioblastoma multiforme. Front Immunol. 2021;11:603911. doi: 10.3389/fimmu.2020.603911 google scholar
• Shoaf ML, Desjardins A. Oncolytic viral therapy for ma-lignant glioma and their application in clinical practice. Neurotherapeutics. 2022;19:1818-1831. google scholar
• Shoaf ML, Desjardins A. Oncolytic viral therapy for ma-lignant glioma and their application in clinical practice. Neurotherapeutics. 2022;19:1818-1831. google scholar
• Qi Z, Long X, Liu J, Cheng P. Glioblastoma microen-vironment and its reprogramming by oncolytic virother-apy. Front Cell Neurosci. 2022;16:819363. doi: 10.3389/fn-cel.2022.819363. google scholar
• Qi Z, Long X, Liu J, Cheng P. Glioblastoma microen-vironment and its reprogramming by oncolytic virother-apy. Front Cell Neurosci. 2022;16:819363. doi: 10.3389/fn-cel.2022.819363. google scholar
• Kamynina M, Tskhovrebova S, Fares J, et al. Oncolytic virus-induced autophagy in glioblastoma. Cancers. 2021;13:3482. doi: 10.3390/cancers13143482 google scholar
• Kamynina M, Tskhovrebova S, Fares J, et al. Oncolytic virus-induced autophagy in glioblastoma. Cancers. 2021;13:3482. doi: 10.3390/cancers13143482 google scholar
• Haddad AF, Young JS, Mummaneni NV, Kasahara N, Aghi MK. Immunologic aspects of viral therapy for glioblastoma and impli-cations for interactions with immunotherapies. J Neuro-Oncol. 2021;152:1-13. google scholar
• Haddad AF, Young JS, Mummaneni NV, Kasahara N, Aghi MK. Immunologic aspects of viral therapy for glioblastoma and impli-cations for interactions with immunotherapies. J Neuro-Oncol. 2021;152:1-13. google scholar
• Ali S, Xia Q, Muhammad T, et al. Glioblastoma therapy: Ratio-nale for a mesenchymal stem cell-based vehicle to carry recom-binant viruses. Stem Cell Rev Rep. 2022;18:523-543. google scholar
• Ali S, Xia Q, Muhammad T, et al. Glioblastoma therapy: Ratio-nale for a mesenchymal stem cell-based vehicle to carry recom-binant viruses. Stem Cell Rev Rep. 2022;18:523-543. google scholar
• Desjardins A, Gromeier M, Herndon JE 2nd, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med. 2018;379:150-161. google scholar
• Desjardins A, Gromeier M, Herndon JE 2nd, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med. 2018;379:150-161. google scholar
• Gromeier M, Lachmann S, Rosenfeld MR, Gutin PH, Wimmer E. Intergeneric poliovirus recombinants for the treatment of ma-lignant glioma. Proc Natl Acad Sci USA. 2000;97:6803-6808., google scholar
• Gromeier M, Lachmann S, Rosenfeld MR, Gutin PH, Wimmer E. Intergeneric poliovirus recombinants for the treatment of ma-lignant glioma. Proc Natl Acad Sci USA. 2000;97:6803-6808., google scholar
• Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370:699-708. google scholar
• Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370:699-708. google scholar
• Hegi ME, Rajakannu P, Weller M. Epidermal growth factor re-ceptor: A re-emerging target in glioblastoma. Curr Opin Neurol. 2012;25:774-779. google scholar
• Hegi ME, Rajakannu P, Weller M. Epidermal growth factor re-ceptor: A re-emerging target in glioblastoma. Curr Opin Neurol. 2012;25:774-779. google scholar
• Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mu-tant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013;340:626-630. google scholar
• Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mu-tant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013;340:626-630. google scholar
• Cancer Genome Atlas Research. Comprehensive genomic char-acterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061-1068. google scholar
• Cancer Genome Atlas Research. Comprehensive genomic char-acterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061-1068. google scholar
• Lee EQ, Kuhn J, Lamborn KR, et al. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 0502. Neuro Oncol. 2012;14:1511-1518. google scholar
• Lee EQ, Kuhn J, Lamborn KR, et al. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 0502. Neuro Oncol. 2012;14:1511-1518. google scholar
• Wen PY, Chang SM, Lamborn KR, et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro Oncol. 2014;16:567-578. google scholar
• Wen PY, Chang SM, Lamborn KR, et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro Oncol. 2014;16:567-578. google scholar
• Chinot OL, Wick W, Mason M, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709-722. google scholar
• Chinot OL, Wick W, Mason M, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709-722. google scholar
• Sandmann T, Bourgon R, Garcia J, et al. Patients with proneural glioblastoma may derive overall survival benefit from the ad-dition of bevacizumab to first-line radiotherapy and temozolo-mide: retrospective analysis of the AVAglio trial. J Clin Oncol. 2015;33:2735-2744. google scholar
• Sandmann T, Bourgon R, Garcia J, et al. Patients with proneural glioblastoma may derive overall survival benefit from the ad-dition of bevacizumab to first-line radiotherapy and temozolo-mide: retrospective analysis of the AVAglio trial. J Clin Oncol. 2015;33:2735-2744. google scholar
• Pilie PG, Tang C, Mills GB, Yap TA. State-of-the-art strategies for targeting the DNA damage response in cancer. Nat Rev Clin Oncol. 2019;16(2):81-104. google scholar
• Pilie PG, Tang C, Mills GB, Yap TA. State-of-the-art strategies for targeting the DNA damage response in cancer. Nat Rev Clin Oncol. 2019;16(2):81-104. google scholar
• Gupta SK, Mladek AC, Carlson BL, et al. Discordant in vitro and in vivo chemopotentiating effects of the PARP inhibitor veliparib in temozolomide-sensitive versus -resistant glioblastoma multi-forme xenografts. Clin Cancer Res. 2014;20(14):3730-3741. google scholar
• Gupta SK, Mladek AC, Carlson BL, et al. Discordant in vitro and in vivo chemopotentiating effects of the PARP inhibitor veliparib in temozolomide-sensitive versus -resistant glioblastoma multi-forme xenografts. Clin Cancer Res. 2014;20(14):3730-3741. google scholar
• Venneti S, Thompson CB. Metabolic reprogramming in brain tumors. Annu Rev Pathol. 2017;12:515-545. google scholar
• Venneti S, Thompson CB. Metabolic reprogramming in brain tumors. Annu Rev Pathol. 2017;12:515-545. google scholar
• Agnihotri S, Golbourn B, Huang X, et al. PINK1 is a nega-tive regulator of growth and the Warburg effect in glioblastoma. Cancer Res. 2016;76(16):4708-4719. google scholar
• Agnihotri S, Golbourn B, Huang X, et al. PINK1 is a nega-tive regulator of growth and the Warburg effect in glioblastoma. Cancer Res. 2016;76(16):4708-4719. google scholar
• Agnihotri S, Mansouri S, Burrell K, et al. Ketoconazole and posaconazole selectively target HK2-expressing glioblastoma cells. Clin Cancer Res. 2019;25(2):844-855. google scholar
• Agnihotri S, Mansouri S, Burrell K, et al. Ketoconazole and posaconazole selectively target HK2-expressing glioblastoma cells. Clin Cancer Res. 2019;25(2):844-855. google scholar
• Villa GR, Hulce JJ, Zanca C, et al. An LXR-cholesterol axis creates a metabolic co-dependency for brain cancers. Cancer Cell. 2016;30(5):683-693. google scholar
• Villa GR, Hulce JJ, Zanca C, et al. An LXR-cholesterol axis creates a metabolic co-dependency for brain cancers. Cancer Cell. 2016;30(5):683-693. google scholar
• Rominiyi O, Vanderlinden A, Clenton SJ, et al. Tumour treat-ing fields therapy for glioblastoma: current advances and future directions. BrJ Cancer. 2021; 124:697-709. google scholar
• Rominiyi O, Vanderlinden A, Clenton SJ, et al. Tumour treat-ing fields therapy for glioblastoma: current advances and future directions. BrJ Cancer. 2021; 124:697-709. google scholar
• Olatunji G, Aderinto N, Adefusi T, et al. Efficacy of tumour-treating fields therapy in recurrent glioblastoma: A narra-tive review of current evidence. Medicine (Baltimore). 2023 102(48):e36421. doi: 10.1097/MD.0000000000036421 google scholar
• Olatunji G, Aderinto N, Adefusi T, et al. Efficacy of tumour-treating fields therapy in recurrent glioblastoma: A narra-tive review of current evidence. Medicine (Baltimore). 2023 102(48):e36421. doi: 10.1097/MD.0000000000036421 google scholar