Neuro-oncology最新文献

{"title":"Cancer Neuroscience: Establishing a home in Neuro-Oncology.","authors":"Shawn L Hervey-Jumper, Michelle Monje, Frank Winkler, David H Gutmann","doi":"10.1093/neuonc/noag129","DOIUrl":"https://doi.org/10.1093/neuonc/noag129","url":null,"abstract":"<p><p>Although neurons innervate all organs in which solid tumors grow, the role of neurons in cancer biology has long been neglected. Over the past decade, numerous studies have elucidated the critical role of the nervous system in cancer pathophysiology, culminating in the birth of Cancer Neuroscience. The recognition that neurons dictate many aspects of tumor biology not only provides new opportunities for therapeutic targeting of these stromal dependencies but also underscores the strong bi-directional relationships between tumors and the nervous system that result in cancer-associated symptomatology. By recognizing the key place of neurons in tumor biology, Cancer Neuroscience has ushered in a new era in which brain cancers should be conceptualized as diseases of dysregulated neurodevelopment, neuroplasticity, and neurophysiological function, usurped to drive brain cancer growth, progression, and therapeutic resistance. Likewise, the nervous system governs the initiation, growth, spread, and survival of most (if not all) extracranial cancers, while also mediating communication from cancers to the brain. Herein, we outline the current state of Cancer Neuroscience and the roles for neuro-oncologists in this new aspect of cancer care as an introduction to an upcoming series of articles in Neuro-Oncology on cellular interactions in the healthy nervous system and in the setting of cancer.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioma and ependymoma through the lens of brain development, stem cells, and plasticity.","authors":"Costanza Lo Cascio, Antoni Martija, Mariella G Filbin, Aparna Bhaduri","doi":"10.1093/neuonc/noag200","DOIUrl":"https://doi.org/10.1093/neuonc/noag200","url":null,"abstract":"<p><p>Brain tumors are increasingly understood as having components of a development organization in which malignant cells leverage neural progenitor programs, lineage hierarchies, and circuit interactions that normally shape the developing brain. This review examines how these principles inform the biology of ependymoma and gliomas across the age spectrum, including H3 K27-altered diffuse midline glioma, H3 G34-mutant diffuse hemispheric glioma, IDH-mutant glioma, and glioblastoma. We highlight how tumor identity reflects developmental timing, regional context, and cell-of-origin competence, while also emphasizing that malignant cells can acquire plasticity beyond their normal counterparts. Across entities, single-cell, spatial, lineage-tracing, and organoid studies reveal progenitor-like compartments that sustain tumor growth, generate heterogeneous malignant states, and interact dynamically with the neural and immune microenvironment. Cancer neuroscience further extends this developmental framework by showing that neuronal activity, synaptic input, and neuromodulatory signaling can regulate tumor proliferation, migration, epigenetic state, and therapeutic response. Together, these findings argue that brain tumors should be viewed not as disorganized cellular masses but as aberrant developmental systems. Defining the developmental dependencies and circuit vulnerabilities of malignant progenitor states may enable more precise therapies that target tumor biology while preserving essential brain function.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of [18F]FET-PET on MRI-Based Radiotherapy Target Volumes in Newly Diagnosed Glioblastoma:Results from the FET-PET in Glioblastoma (FIG) Study TROG 18.06.","authors":"E-S Koh, R J Francis, G Ninatti, I Ruisi, M A Ebert, E Lau, A Whitehead, J Descallar, E H Barnes, S T Lee, E L Thomas, M B Pinkham, M Back, S P Ng, N Bucknell, H K Gan, O Cook, R Dykyj, A Moore, S Porter, Patricia Banyer, F E Scott, D L Bailey, N Barry, T Akhurst, R Alipour, A Bece, C Bettingdon, S Beuzeville, J H Chang, B Chua, C Clark, J Croker, S Gill, P Gorayski, E Hsiao, K Jung, S Khan, D Krishna, I Kirkwood, H Le, P Lin, T Ly, M McGuiness, S Ngai, D A Pattison, C Phillips, A P Pullar, G Schembri, J Sia, F Syed, P Thomas, W Vallat, M Wada, D Wong, J Yap, T C Yeow, A K Nowak, F Foroudi, M Rosenthal, P Roach, L Adda, R De Abreu Lourenco, B A Moffat, C Brighi, A Lasocki, L Holloway, M Fay, A M Scott","doi":"10.1093/neuonc/noag229","DOIUrl":"https://doi.org/10.1093/neuonc/noag229","url":null,"abstract":"<p><strong>Background: </strong>The FET-PET in Glioblastoma (FIG) study (TROG 18.06) assessed the impact of adding FET-PET to MRI on radiotherapy gross tumor volume delineation in newly diagnosed glioblastoma.</p><p><strong>Methods: </strong>This multicenter prospective phase 2 study evaluated participants with newly diagnosed glioblastoma IDH-wildtype undergoing post-operative MRI and FET-PET imaging before adjuvant radiotherapy, delivered according to standard MRI-based planning. The FET-PET-positive biological tumor volume (BTV) was used to derive the Hybrid (FET-PET+MRI) gross tumor volume (Hybrid-GTV). Primary outcomes were: 1) BTV excluded from the GTV defined on MRI alone (MR-GTV); 2) Hybrid-GTV excluded from the MR-GTV with both comparisons analyzed by non-overlap volume (cm3 and %), dosimetry (D98 and V95) and spatial similarity metrics; 3) clinically meaningful change in GTV non-overlap percentage volume with the addition of FET-PET.</p><p><strong>Results: </strong>There were 172 participants recruited, n = 140 evaluable. Median BTV was 23.1 cm3, median MR-GTV was 32.1 cm3, and median Hybrid-GTV was 46.0 cm3. Hybrid-GTV was significantly larger than the MR-GTV (p < 0.001), with a larger Hybrid-GTV observed in 83% of cases. Comparing BTV to MR-GTV, median non-overlap volume was 10.1 cm3 and non-overlap percentage volume 53.5%. Comparing Hybrid-GTV to MR-GTV, median non-overlap volume was 14.9 cm3 and non-overlap percentage volume 33.9%. D98 and V95 were lower for the Hybrid-GTV than for the MR-GTV, suggesting lower dose coverage. Applying a > 20% non-overlap percentage volume threshold, 76% of participants had a meaningful change in GTV with the addition of FET-PET.</p><p><strong>Conclusion: </strong>FET-PET differed significantly from MRI-based GTV delineation, with its incorporation leading to a clinically meaningful change in GTV in the majority of participants.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentially inappropriate care at the end of life in patients with glioblastoma: A single-center observational cohort study.","authors":"Robin M Pieterman, Esmée K J van der Poort, Monique C M Baas-Thijssen, Matthijs van der Meulen, Erik W van Zwet, Yvette M van der Linden, Johan A F Koekkoek","doi":"10.1093/neuonc/noag198","DOIUrl":"https://doi.org/10.1093/neuonc/noag198","url":null,"abstract":"<p><strong>Background: </strong>Timely integration of palliative care is critical in the management of patients with glioblastoma. This study evaluated the frequency and determinants of potentially inappropriate care in the final 3 months of life on population level.</p><p><strong>Methods: </strong>Patient characteristics and healthcare utilization were extracted from medical records for deceased patients diagnosed with glioblastoma, who survived at least 3 months after diagnosis and received routine care at a single tertiary hospital between January 2015 and February 2026. Potentially inappropriate care was defined as the proportion of patients with any of these indicators in the final 3 months of life: ≥2 emergency department visits, ≥2 hospital admissions, >14 consecutive hospitalization days, intensive care unit admission, chemotherapy administration, or in-hospital death. Logistic regression analyses were performed to identify factors associated with receiving potentially inappropriate care.</p><p><strong>Results: </strong>The cohort included 310 patients (median age 66 [IQR 56-72], 60% male), of whom 22% (n = 67/310) received potentially inappropriate care in the final 3 months of life. Chemotherapy was the main driver (n = 58/67, 87%), followed by ≥2 hospital admissions (n = 10/67, 15%) and in-hospital death (n = 9/67, 13%). Older patients (OR 0.97, 95% CI, 0.94-0.99) or those with an unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter (OR 0.42, 95% CI, 0.23-0.75) were less likely to receive potentially inappropriate care.</p><p><strong>Conclusion: </strong>One in 5 patients with glioblastoma received potentially inappropriate care at the end of life, predominantly through chemotherapy. Younger patients and those with methylated MGMT promoters were most affected. Identification of patients at risk may support targeted palliative care interventions.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomics for prognostic stratification in newly diagnosed primary central nervous system lymphoma.","authors":"Tamara Künzle, Dora Herzi, Clara Boer Wigman, Lucas Rincon de la Rosa, Lucia Nichelli, Isaias Hernandez-Verdin, Angel Escamilla-Ramírez, Jérôme Paillassa, Renata Ursu, Stefania Cuzzubbo, Frédéric Davi, Magali Le Garff-Tavernier, Guido Ahle, Laurence Schenone, Carole Soussain, Sylvain Choquet, Yannick Marie, Bertrand Mathon, Clovis Adam, Caroline Houillier, Khê Hoang-Xuan, Maks Ovsjanikov, Agustí Alentorn","doi":"10.1093/neuonc/noag190","DOIUrl":"https://doi.org/10.1093/neuonc/noag190","url":null,"abstract":"<p><strong>Background: </strong>Baseline biomarkers anticipating outcome in primary central nervous system lymphoma (PCNSL) are limited, and classical scores rely on clinical variables alone. We present a plasma proteomic framework for prognostic stratification of newly diagnosed PCNSL.</p><p><strong>Methods: </strong>Baseline plasma from 162 newly diagnosed PCNSL patients (French LOC network; training n=84; test n=78) was profiled using Olink Reveal (1,007 proteins). Consensus k-means clustering applied to the training proteome was projected to the test cohort, evaluated for immune-signature enrichment, and assessed by multivariable Cox regression. An elastic-net classifier predicted early treatment failure, evaluated by held-out and nested cross-validated AUC.</p><p><strong>Results: </strong>Clustering identified 2 proteomic states, Inflamed and Non-inflamed plasma, that replicated in the test cohort. The Inflamed state was enriched for pre-specified immune signatures, most strongly an Innate/Inflammatory signature. High Innate/Inflammatory scores marked shorter overall (OS) and progression-free survival (PFS) in training (log-rank P=.0014 OS, P=.0037 PFS) and test (P=5.4×10⁻⁴ OS, P=.0014 PFS), remaining significant after adjustment for MSKCC class and sex (test OS HR 2.51, P=.0022). Combining signatures with clinical variables improved test discrimination, most clearly for PFS (C-index 0.68 vs. 0.60). A supervised classifier predicted early treatment failure (PFS < 9 months) at test AUC 0.71, driven by the immune signatures rather than a whole-proteome search.</p><p><strong>Conclusions: </strong>Plasma proteomics identifies a reproducible Inflamed state in PCNSL associated with shorter OS and PFS that improves discrimination beyond clinical scores and stratifies the risk of early treatment failure. These findings support prospective evaluation of a focused innate-inflammatory plasma panel for risk stratification.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Cell Engager Therapy for Brain Cancer.","authors":"Daan A Sluijter, Rianne van Garderen, Ilse van Haveren, Jan Meeldijk, Sandra Crnko, Thijs Koorman, Toine Ten Broeke, Michael Y Schakelaar, Niels Bovenschen","doi":"10.1093/neuonc/noag227","DOIUrl":"https://doi.org/10.1093/neuonc/noag227","url":null,"abstract":"<p><p>Improving outcomes for patients with brain tumors remains a formidable challenge. Patient survival is often considered very poor even though standard first line treatments include surgery, radiotherapy, and chemotherapy. These therapies often have detrimental side effects on brain functions and do not suffice when tumors advance and metastasize, prompting the need for new treatment modalities. Recent innovations in antibody-based immunotherapies may complement brain cancer treatment. Biotechnical engineering platforms yield new antibody-inspired biomolecules for optimal engagement of specific and tumor-associated antigens, which also recruit and elicit immune effector cell functions. Here, we review current advances on multi-specific immune cell engagers for brain tumor treatment and provide novel insights into overcoming existing challenges.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Murine modeling of IDH-mutant 1p/19q-codeleted oligodendroglioma reveals genotype specific phenotypes.","authors":"Ipsita G Kundu, Nicolas Toro, Aaron Y Mochizuki, Jaldeep Langhnoja, Rithvik V Ayyagari, James C Cronk, Sarah M Reel, Phonepasong Arounleut, Luis E Tron Esqueda, Christine E Fuller, Pavithra Viswanath, Amy B Heimberger, Craig M Horbinski, Timothy N Phoenix","doi":"10.1093/neuonc/noag228","DOIUrl":"10.1093/neuonc/noag228","url":null,"abstract":"<p><strong>Background: </strong>Oligodendroglioma is a primary central nervous system tumor classified by the presence of isocitrate dehydrogenase (IDH) mutations and codeletion of 1p/19q. A lack of faithful preclinical model systems for this disease has limited progress in understanding the biology of this genetically unique subtype of adult diffuse-type glioma and in developing new effective therapies. To address this unmet need, we sought to establish a mouse model that faithfully recapitulates the genetic and phenotypic features of human IDH-mutant 1p/19q-codeleted oligodendroglioma.</p><p><strong>Methods: </strong>We performed in utero electroporation to introduce distinct combinations of genetic alterations and evaluated their potential to form tumors. Resulting tumors were characterized by histology, metabolite profiling, RNA-sequencing and single-cell RNA sequencing.</p><p><strong>Results: </strong>We identified co-expression of IDH1R132H and PIK3CAE545K together with loss of Cic, Fubp1 and Cdkn2a (termed OligoCdkn2a) as the optimal genetic combination to drive fully penetrant tumors that histologically resemble human grade II/III IDH-mutant 1p/19q-codeleted oligodendroglioma. Substituting Cdkn2a loss with Trp53 deletion decreased latency and shifted tumors toward high-grade astrocytoma histology. OligoCdkn2a tumors displayed metabolic and transcriptional changes associated with IDH and CIC mutations, and single-cell sequencing identified a bias towards oligodendrocyte differentiation compared to an IDH wild-type glioblastoma mouse model.</p><p><strong>Conclusions: </strong>To our knowledge, OligoCdkn2a tumors represent the first autochthonous, genetically engineered mouse model to recapitulate the genetic, histological and transcriptional features of human IDH-mutant 1p/19q-codeleted oligodendrogliomas. This model will provide a valuable platform to further dissect mechanisms of tumorigenesis and test novel therapeutic strategies for this molecularly distinct glioma subtype.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Spatiotemporal Evolution of Radiation Resistance in Glioblastoma.","authors":"Lingxiang Wu, Lei Cheng, Bin Huang, Runheng Huang, Ravesanker Ezhilarasan, Junxia Zhang, Wei Wu, Guojing Wu, Benqing Yu, Lindsey D Goodman, Ananya Jambhale, Baoli Hu, Apeng Chen, Mengyan Zhu, Min Wu, Peng Xia, Quanzhong Liu, Miao Yu, Zheng Zhao, Zhangchun Cheng, Ning Wang, Fan Lin, Fengqi Zhou, Ze-Yan Zhang, Yingwen Ding, Jian Chen, Xu Qian, Xiuxing Wang, Yu Shi, Joy Gumin, Krishna Bhat, W K Alfred Yung, Kenneth D Aldape, Roel G W Verhaak, Frederick F Lang, Yongping You, Jiankai Yang, Qianghu Wang, Erik P Sulman","doi":"10.1093/neuonc/noag209","DOIUrl":"https://doi.org/10.1093/neuonc/noag209","url":null,"abstract":"<p><strong>Background: </strong>Although radiation therapy (RT) remains one of the most effective treatments for patients with the lethal brain tumor glioblastoma (GBM), quite a number of patients show resistance or relapse shortly after RT. There is an urgent need to uncover the temporal and spatial dynamics of RT resistance during tumor progression and treatment.</p><p><strong>Methods: </strong>The radio-resistance signature score (RRSS) was calculated by utilizing glioma sphere-forming cells (GSCs) which recapitulate the transcriptomic landscape of GBM.</p><p><strong>Results: </strong>RRSS can assess the RT response on both cell lines and GBM patients. Both transdifferentiated and irradiated glioma cells show increased radiation resistance, demonstrating that the recurrent GBM may acquire resistance along with cell differentiation and selective advantage during treatment. Moreover, RRSS of the marginal tumors is found to be higher than that of core tumors (Wilcoxon's rank-sum test, p-value<0.01). The infiltration of macrophages was significantly associated with radiation resistance (p-value<0.01), which was further validated by single-cell RNAseq based experiments and clonogenic assays. Moreover, we demonstrated that IL1B, a pro-inflammatory cytokine secreted by macrophages, could enhance the radiation resistance of tumor cells.</p><p><strong>Conclusions: </strong>Our study revealed the spatiotemporal evolution of radiation resistance of GBM, and shed light on the development of novel adjuvant therapeutic strategies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EFTUD2-Regulated Alternative Splicing of MSH5 Drives Radioresistance in Recurrent IDH-Mutant Glioma.","authors":"Qiu He, Runxin Wu, Xiaozhou Yu, Xiao Song, Maya Walker, Deanna Tiek, Tongchao Jiang, Xiao-Nan Li, Chengtao Her, Bo Hu, Shi-Yuan Cheng","doi":"10.1093/neuonc/noag225","DOIUrl":"https://doi.org/10.1093/neuonc/noag225","url":null,"abstract":"<p><strong>Background: </strong>Recurrent IDH-mutant gliomas frequently acquire increased radioresistance, leading to poorer outcomes. Their underlying mechanisms, however, remain largely unknown. We hypothesize that dysregulated RNA alternative splicing (AS) during IDH-mutant glioma recurrence contributes to the enhanced radioresistance by influencing critical cellular pathways.</p><p><strong>Methods: </strong>RNA sequencing of paired primary and recurrent IDH-mutant gliomas were analyzed to identify recurrence-associated AS events. Functional effects were assessed in patient-derived glioma stem cells using RNA interference and CRISPR-dCas13-mediated isoform switching. Candidate upstream RNA-binding proteins and antisense oligonucleotide (ASO)-based therapeutic strategies were evaluated in vitro and in vivo.</p><p><strong>Results: </strong>We identified differentially spliced MutS homolog 5 (MSH5) isoforms between primary and recurrent IDH-mutant gliomas. Primary gliomas predominantly expressed an exon 11/12-skipped MSH5 transcript, whereas recurrent tumors largely retained the full-length isoform. Exon 11/12 skipping introduced a premature termination codon, leading to nonsense-mediated decay and diminished MSH5 expression in primary tumors. Further analyses identified elongation factor Tu GTP binding domain containing 2 (EFTUD2) as an upstream splicing regulator that was upregulated in recurrent tumors and promoted exon 11/12 inclusion, thereby maintaining MSH5 expression and enhancing the repair of radiation-induced DNA double-strand breaks. Inducing MSH5 exon 11/12 skipping with CRISPR-dCas13 or inhibiting EFTUD2 with ASOs reduced MSH5 expression, impaired DNA repair, and sensitized recurrent IDH-mutant glioma to radiotherapy in vitro and in vivo.</p><p><strong>Conclusions: </strong>These findings identify an EFTUD2-MSH5 splicing axis that contributes to radioresistance in recurrent IDH-mutant glioma. Therapeutic disruption of this splicing program may represent a strategy to enhance the radiation response in recurrent IDH-mutant glioma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional clustering within glioblastoma identifies a network-integrated subtype with improved survival.","authors":"Danting Zeng, Abraham Z Snyder, Ki Yun Park, Benjamin T Acland, Joshua S Shimony, Eric C Leuthardt","doi":"10.1093/neuonc/noag223","DOIUrl":"https://doi.org/10.1093/neuonc/noag223","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is traditionally viewed as disrupting brain network connectivity. Recent evidence of tumor-neuron synaptic interactions suggests gliomas may actively engage with the brain. We hypothesized that GBM tumors contain functionally distinct intratumoral subregions that differentially couple with resting-state networks (RSNs) and carry prognostic significance.</p><p><strong>Methods: </strong>We applied fuzzy c-means clustering to resting-state fMRI data from 190 GBM patients to identify and count the number of intratumoral functional subregions. We used the participation ratio, a PCA-derived measure of signal dimensionality, as a continuous variable complement to cluster number. Cluster-level BOLD time series were correlated with seven canonical RSNs and compared to tumor location-matched voxels in 347 healthy subjects. Associations with survival and preoperative seizures were evaluated using Kaplan-Meier analysis, restricted mean survival time (RMST), multivariable Cox proportional hazards modeling, and multivariable logistic regression.</p><p><strong>Results: </strong>Fifty-two of 190 GBMs exhibited multiple intratumoral functional clusters. Multi-cluster tumors were associated with longer survival and higher seizure prevalence. Elevated RSN coupling was more prevalent in multi-cluster tumors as compared to single-cluster tumors, with elevated coupling strongly predicting multi-cluster status. Distinct clusters often showed preferential coupling to different RSNs.</p><p><strong>Conclusions: </strong>A subset of GBM contains functionally distinct subregions that selectively engage large-scale brain networks, a pattern associated with favorable survival and increased seizure risk. These findings support a model in which certain tumors function as active participants within neurovascular networks, indicating a novel network-integrated subtype of GBM with implications for prognosis and disease staging.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}