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Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions
Open accessAbstract
Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
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“For this patient population, there is currently no efficacious treatment option available [4].”
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“The current standard of care for GBM includes surgical resection and post-surgery radiotherapy with or without temozolomide (TMZ) chemotherapy [4, 5].”
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“Despite standard of care treatment, GBM recurrence is inevitable and there is no agreed salvage therapy post-recurrence [4, 5].”
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Glioblastoma: Relationship between Metabolism and Immunosuppressive Microenvironment
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“Although numerous diagnostic or predictive of response biomarkers have been identified, such as isocitrate dehydrogenase (IDH) mutation or O6-methylguanine DNA methylation status [5], treatment has not improved in parallel over the last three decades [5].”
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Imaging Tumor-Infiltrating Lymphocytes in Brain Tumors with [64Cu]Cu-NOTA-anti-CD8 PET
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“While immune responses can be elicited to antigens that are expressed in the central nervous system (2, 3), attempts to treat GBM with antibodies blocking the PD-1 pathway or other immunedirected therapies have failed to improve patient survival (4).”
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“Today, the methylating triazene derivative TMZ is recommended as first-line therapy in IDH wild-type glioblastoma by the European Association of Neuro-Oncology (EANO) and the Society of Neuro-Oncology [11,12].”
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Ser, M. H., Webb, M., Sener, U. T., & Campian, J. L. (2023) · Journal of Immunotherapy and Precision Oncology · doi:10.36401/jipo-23-34 · Cited by 51
Spatial analysis of recurrent glioblastoma reveals perivascular niche organization
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“Loss of focal adhesion kinase (FAK) inhibits epidermal growth factor receptor-dependent migration and induces aggregation of nh(2)-terminal FAK in the nuclei of apoptotic glioblastoma cells.”
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Self-citationTumor microenvironment in glioblastoma: The central role of the hypoxic–necrotic core
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Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma
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“- 5 1 INTRODUCTION Patients with glioblastoma survive for 12-15 months on average despite treatment with surgery, focal irradiation, alkylating chemotherapy and tumor treating fields (1-4).”
BackgroundSelf-citationPleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
Dean, P. T., & Hooks, S. B. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1116014 · Cited by 43
Laukamp, K. R., Terzis, R., Werner, J., Galldiks, N., Lennartz, S., Maintz, D. C., Reimer, R. P., Fervers, P., Gertz, R. J., ten Persigehl, T., et al. (2024) · Radiology · doi:10.1148/radiol.232640 · Cited by 41
TREM2 is associated with tumor immunity and implies poor prognosis in glioma
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“Currently, standard treatment approaches for GBM are surgical methods, radiotherapies, and temozolomide (TMZ) chemotherapy [3].”
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BackgroundThe complexities underlying epilepsy in people with glioblastoma
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“However, no treatments for rGBM have been demonstrated to improve overall survival (OS) in phase III randomized clinical trials (RCTs) [2].”
BackgroundIs PROTAC technology really a game changer for central nervous system drug discovery?
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“Glioblastoma is an aggressive, malignant brain tumor that typically leads to death within 15–18 months [46].”
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“Glioblastoma (GBM) is the most malignant brain tumor, with high morbidity and mortality.[1] In the United States (US) population, GBM is associated with advanced age and male sex[2] and is more frequently observed in Caucasians than in other ethnicities.”
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“Standard of care treatment includes maximal safe surgery followed by chemoradiotherapy with temozolomide [5].”
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“GBM has a poor prognosis with a mean survival of 15–18 months post-diagnosis [2,4].”
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Self-citationResearch progress of drug resistance mechanism of temozolomide in the treatment of glioblastoma
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Connexin 43 and Sonic Hedgehog Pathway Interplay in Glioblastoma Cell Proliferation and Migration
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“Despite the multimodal and synergistic approaches, combining surgical, pharmacological and radiotherapeutic strategies, glioblastoma (GBM) is still the most lethal brain tumor, characterized by high rate of recurrences and a dismal prognosis [1,2].”
BackgroundBooth, T. C., Wiegers, E. C., Warnert, E. A. H., Schmainda, K. M., Riemer, F., Nechifor, R. E., Keil, V. C., Hangel, G. J., Figueiredo, P., Álvarez‐Torres, M. D. M., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.811425 · Cited by 36
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“First-line clinical treatment of GBM remains surgical resection followed by radiation therapy [15], despite studies suggesting that tumors tend to have heterogeneous environments [16, 17].”
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Progress of nanoparticle drug delivery system for the treatment of glioma
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Survival of brain tumour patients with epilepsy
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Self-citationPrognostic significance of therapy-induced myelosuppression in newly diagnosed glioblastoma
Rhun, É. L., Oppong, F. B., Vanlancker, M., Stupp, R., Nabors, B., Chinot, O. L., Wick, W., Preusser, M., Gorlia, T., & Weller, M. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac070 · Cited by 34
Self-citationA 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth
Tung, Y., Chen, Y., Derr, K., Wilson, K. M., Song, M. J., & Ferrer, M. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202302831 · Cited by 34
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“These inflammatory cytokines promote angiogenesis and tumor progression by inhibiting T cells and natural killer (NK) cells [41].”
Pharmacotherapeutic Treatment of Glioblastoma: Where Are We to Date?
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Acetyl-CoA Synthetase 2 as a Therapeutic Target in Tumor Metabolism
Liu, M., Liu, N., Wang, J., Fu, S., Wang, X., & Chen, D. (2022) · Cancers · doi:10.3390/cancers14122896 · Cited by 39
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“The median survival for GBM patients is 3 months following surgical resection only, improving to 8 and 15–18 months when radiotherapy [19] or radiotherapy plus temozolomide chemotherapy, respectively, are used as adjuncts to surgery [20,21].”
BackgroundAquilanti, E., Kageler, L., Watson, J., Baird, D. M., Jones, R. E., Hodges, M., Szegletes, Z. M., Doench, J. G., Strathdee, C. A., McFaline-Figueroa, J. R., et al. (2023) · Neuro-Oncology · doi:10.1093/neuonc/noad024 · Cited by 33
Self-citationHypoxia-induced galectin-8 maintains stemness in glioma stem cells via autophagy regulation
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Recent advances in targeted drug delivery for the treatment of glioblastoma
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Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance
D’Aprile, S., Denaro, S., Gervasi, A., Vicario, N., & Parenti, R. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1535073 · Cited by 36
Immune checkpoint inhibitors in GBM
Lee, E. Q. (2021) · Journal of Neuro-Oncology · doi:10.1007/s11060-021-03859-8 · Cited by 35
Self-citationMultiomic screening of invasive GBM cells reveals targetable transsulfuration pathway alterations
Garcia, J. H., Akins, E. A., Jain, S., Wolf, K. J., Zhang, J., Choudhary, N. R., Lad, M., Shukla, P. D., Rios, J., Seo, K., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci170397 · Cited by 34
Ricciardi, L., Manini, I., Cesselli, D., Trungu, S., Piazza, A., Mangraviti, A., Miscusi, M., Raco, A., & Ius, T. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.884158 · Cited by 32
Bühler, M., Yi, X., Ge, W., Blattmann, P., Rushing, E. J., Reifenberger, G., Felsberg, J., Yeh, C. D., Corn, J. E., Regli, L., et al. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac169 · Cited by 34
Self-citationHosseini, S. A., Hosseini, E., Hajianfar, G., Shiri, I., Servaes, S., Rosa‐Neto, P., de Godoy, L. L., Nasrallah, M. P., O’Rourke, D. M., Mohan, S., et al. (2023) · Cancers · doi:10.3390/cancers15030951 · Cited by 32
“Glioblastomas (GBMs) are devastating and universally fatal brain cancers in adults despite advancements in diagnostic and therapeutic strategies [1].”
BackgroundBetulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives
Fernandes, S., Vieira, M., Prudêncio, C., & Ferraz, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042108 · Cited by 31
“…( ATRX ), and tumor protein P53 ( TP53 ) gene mutations, epidermal growth factor receptor ( EGFR ) gene amplification, loss of heterozygosity of the phosphatase and tensin homolog ( PTEN ) gene and telomerase reverse transcriptase ( TERT ) promoter mutation [47,49,54,55].”
BackgroundInfluentialViruses in glioblastoma: an update on evidence and clinical trials
Gunasegaran, B., Ashley, C. L., Marsh‐Wakefield, F., Guillemin, G. J., & Heng, B. (2024) · BJC Reports · doi:10.1038/s44276-024-00051-z · Cited by 32
“A considerable number of GB patients do not exhibit identi fi able risk factors for tumour development [6].”
BackgroundBlood-brain barrier penetrating nanosystems enable synergistic therapy of glioblastoma
Sun, Y., Li, M., Zheng, M., Zou, Y., & Shi, B. (2024) · Nano Today · doi:10.1016/j.nantod.2024.102310 · Cited by 31
Targeting drug resistance in glioblastoma (Review)
Sherman, J. H., Bobak, A., Arsiwala, T. A., Lockman, P. R., & Aulakh, S. (2024) · International Journal of Oncology · doi:10.3892/ijo.2024.5668 · Cited by 34
Lim-Fat, M. J., Bennett, J., Ostrom, Q. T., Touat, M., Franceschi, E., Schulte, J. D., Bindra, R. S., Fangusaro, J., Dhall, G., Nicholson, J. C., et al. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae186 · Cited by 36
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Self-citationLim-Fat, M. J., Youssef, G., Touat, M., Iorgulescu, J. B., Whorral, S., Allen, M., Rahman, R. M., Chukwueke, U. N., McFaline-Figueroa, J. R., Nayak, L., et al. (2021) · Neuro-Oncology · doi:10.1093/neuonc/noab282 · Cited by 31
Self-citationRahman, R. M., Polley, M. C., Alder, L., Brastianos, P. K., Anders, C. K., Tawbi, H. A., Mehta, M. P., Wen, P. Y., Geyer, S. M., de Groot, J., et al. (2023) · The Lancet Oncology · doi:10.1016/s1470-2045(23)00005-0 · Cited by 31
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“Glioblastoma multiforme (GBM) is considered the most common, malignant, primary brain tumor, which tends to relapse in some patients, even after an aggressive combination of therapies due to the molecular heterogeneity of the disease [1 – 3].”
BackgroundImpact of recurrence pattern in patients undergoing a second surgery for recurrent glioblastoma
Pasqualetti, F., Montemurro, N., Desideri, I., Loi, M., Giannini, N., Gadducci, G., Malfatti, G., CANTARELLA, M., Gonnelli, A., MONTRONE, S., et al. (2021) · Acta Neurologica Belgica · doi:10.1007/s13760-021-01765-4 · Cited by 30
Pibuel, M. A., Poodts, D., Díaz, M., Molinari, Y. A., Franco, P. G., Hajos, S. E., & Lompardía, S. L. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00672-0 · Cited by 30
“Although new data obtained of phase III clinical trials indicate some improvement in the overall survival time [29], most of the data available showed that under the current therapy that includes surgical resection,”
BackgroundSaha, S., Zhang, Y., Wilson, B., Abounader, R., & Dutta, A. (2021) · Journal of Cell Science · doi:10.1242/jcs.259306 · Cited by 32
Glioblastoma — treatment and obstacles
Cantídio, F. S., Gil, G. O. B., Queiroz, I. N., & Regalin, M. (2022) · Reports of Practical Oncology & Radiotherapy · doi:10.5603/rpor.a2022.0076 · Cited by 30
“The malignant glioma is derived from the neuroglial stem cells or progenitor cells [5] and neoplasia originate from somatic molecular defects in three pathways: initiating tumor growth, evading senescence, and enabling immortal growth [6].”
BackgroundYang, H., Liu, X., Zhu, X., Zhang, M., Wang, Y., Ma, M., & Lv, K. (2022) · iScience · doi:10.1016/j.isci.2022.104952 · Cited by 30
Artesunate in glioblastoma therapy: Case reports and review of clinical studies
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Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies
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Association of plasma cell-free DNA with survival in patients with IDH wild-type glioblastoma
Bagley, S. J., Till, J. E., Abdalla, A., Sangha, H. K., Yee, S. S., Freedman, J. M., Black, T. A., Hussain, J., Binder, Z. A., Brem, S. S., et al. (2021) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdab011 · Cited by 29
“As of the July 28, 2020 data cutoff, pre-operative blood samples had been collected from 96 consecutive patients, all of whom had tumors determined to be IDH wild-type; 9 were taken off study because histopathology did not confirm GBM, and 25 were excluded because they received experimental therapies and/or tumor-trea…”
BackgroundInfluentialCollet, S., Guillamo, J., Berro, D. H., Chakhoyan, A., Constans, J., Lechapt, E., Derlon, J.-M., Hatt, M., Visvikis, D., Guillouet, S., et al. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.249524 · Cited by 29
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Self-citationGalectins as Emerging Glyco-Checkpoints and Therapeutic Targets in Glioblastoma
Videla-Richardson, G. A., Morris-Hanon, O., Torres, N. I., Esquivel, M. I., Vera, M. B., Ripari, L. B., Croci, D. O., Sevlever, G. E., & Rabinovich, G. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010316 · Cited by 29
“This progress has not fully impacted the survival rate of malignant gliomas, which remains similar to several decades ago [4].”
ResultVanbilloen, W. J. F., Rechberger, J. S., Anderson, J. B., Nonnenbroich, L. F., Zhang, L., & Daniels, D. J. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071804 · Cited by 33
“Most brain tumors have proved challenging to treat, due in large part to the molecular features of these tumors, which frequently work in concert to impede advancements in therapy [10].”
BackgroundZhang, H., Fan, X., Zhang, J., Wei, Z., Feng, W., Hu, Y., Ni, J., Yao, F., Zhou, G., Wan, C., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1143688 · Cited by 29
Karschnia, P., Young, J. S., Wijnenga, M. M. J., Sciortino, T., Teske, N., Corell, A., Wagner, A., Youssef, G., Park, Y. W., Häni, L., et al. (2025) · The Lancet Oncology · doi:10.1016/s1470-2045(25)00534-0 · Cited by 32
Self-citationImmune Microenvironment and Immunotherapies for Diffuse Intrinsic Pontine Glioma
Chen, Y., Zhao, C., Li, S., Wang, J., & Zhang, H. (2023) · Cancers · doi:10.3390/cancers15030602 · Cited by 28
Novel approaches to targeting gliomas at the leading/cutting edge
Schüpper, A. J., & Hadjipanayis, C. G. (2023) · Journal of neurosurgery · doi:10.3171/2023.1.jns221798 · Cited by 27
Current Status and Challenges of Oncolytic Virotherapy for the Treatment of Glioblastoma
Webb, M., Sener, U. T., & Vile, R. G. (2023) · Pharmaceuticals · doi:10.3390/ph16060793 · Cited by 27
“Though systemic therapies such as bevacizumab and lomustine are frequently administered, to date, no intervention for recurrent GBM has been associated with a clear survival benefit in a large-scale clinical trial [4].”
Metadata
- Authors
- Wen, P. Y., Weller, M., Lee, E. Q., Alexander, B. M., Barnholtz-Sloan, J. S., Barthel, F. P., Batchelor, T. T., Bindra, R. S., Chang, S. M., Chiocca, E. A., Cloughesy, T. F., DeGroot, J. F., Galanis, E., Gilbert, M. R., Hegi, M. E., Horbinski, C., Huang, R. Y., Lassman, A. B., Le Rhun, E., Lim, M., Mehta, M. P., Mellinghoff, I. K., Minniti, G., Nathanson, D., Platten, M., Preusser, M., Roth, P., Sanson, M., Schiff, D., Short, S. C., Taphoorn, M. J. B., Tonn, J.-C., Tsang, J., Verhaak, R. G. W., von Deimling, A., Wick, W., Zadeh, G., Reardon, D. A., Aldape, K. D., & van den Bent, M. J.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Zurich (CH)
- Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA
- The Jackson Laboratory for Genomic Medicine (US)
- Yale University (US)
- University of California, San Francisco (US)
- University of California, Los Angeles (US)
- The University of Texas MD Anderson Cancer Center (US)
- Mayo Clinic (US)
- National Institutes of Health (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Northwestern University (US)
- NewYork–Presbyterian Hospital (US)
- University of Lille, Inserm, Neuro-oncology, General and Stereotaxic Neurosurgery service, University Hospital of Lille, Lille, France; Breast Cancer Department, Oscar Lambret Center, Lille, France and Department of Neurology & Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland
- Johns Hopkins University (US)
- Miami Cancer Institute, Miami, Florida, USA
- Memorial Sloan Kettering Cancer Center (US)
- University of Siena (IT)
- Heidelberg University (DE)
- Medical University of Vienna (AT)
- Centre National de la Recherche Scientifique (FR)
- University of Virginia (US)
- University of Leeds (GB)
- Leiden University Medical Center (NL)
- LMU Klinikum (DE)
- Neuropathology and Clinical Cooperation Unit Neuropathology, University Heidelberg and German Cancer Center, Heidelberg, Germany
- Princess Margaret Cancer Centre (CA)
- National Cancer Institute (US)
- Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
- Corresponding author
- Wen, Patrick Y
- Weller, Michael
- ORCID
- Wen, Patrick Y
- Weller, Michael
- Lee, Eudocia Quant
- Alexander, Brian M
- Barthel, Floris P
- Batchelor, Tracy T
- Bindra, Ranjit S
- Chang, Susan M
- Chiocca, E Antonio
- Cloughesy, Timothy F
- Galanis, Evanthia
- Gilbert, Mark R
- Hegi, Monika E
- Horbinski, Craig
- Huang, Raymond Y
- Lassman, Andrew B
- Lim, Michael
- Mehta, Minesh P
- Mellinghoff, Ingo K
- Minniti, Giuseppe
- Nathanson, David
- Platten, Michael
- Preusser, Matthias
- Roth, Patrick
- Sanson, Marc
- Schiff, David
- Short, Susan C
- Taphoorn, Martin J B
- Tonn, Joerg-Christian
- Tsang, Jonathan
- Verhaak, Roel G W
- Wick, Wolfgang
- Zadeh, Gelareh
- Reardon, David A
- Aldape, Kenneth D
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-04-24
- Volume
- 22
- Issue
- 8
- Pages
- 1073-1113
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- PMC
- PMC7594557
- OpenAlex
- W3020099303
- Cited by
- 1,168
- References
- 334
- Citations by year
- 2026: 166 · 2025: 215 · 2024: 242 · 2023: 204 · 2022: 194 · 2021: 118 · 2020: 28
- FWCI
- 71.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Neuro-Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- IRIS (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- HAL (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Funders
- University of Leeds
- National Institutes of Health (UL1TR001863)
- National Cancer Institute (P01CA069246, P30CA008748, P50CA211015, P30CA016672, P01CA163205)
- National Institute of Neurological Disorders and Stroke (R35NS105109)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Keywords
- glioblastoma, IDH-wildtype glioblastoma, adult brain tumors, molecular pathogenesis, targeted therapy, DNA damage response, metabolic therapy, immunotherapy, viral therapy, treatment management
- MeSH terms
- Brain Neoplasms, Glioblastoma, Humans, Isocitrate Dehydrogenase, Randomized Controlled Trials as Topic, Clinical Trials, Phase III as Topic, Chemoradiotherapy
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