Neuro-oncology最新文献

{"title":"Emergence of inactivating NOTCH1 mutations in an IDH-mutant astrocytoma with clinical resistance to vorasidenib treatment.","authors":"Tomoyuki Nakano, Nicholas A Jessop, Charlotte I Wang, Maria Martinez-Lage, Itay Tirosh, Mario L Suva, Hiroaki Wakimoto, Daniel P Cahill, Christine Lu-Emerson, Julie J Miller","doi":"10.1093/neuonc/noag174","DOIUrl":"https://doi.org/10.1093/neuonc/noag174","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195712","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":"Hijacking Developmental Immunity: Inflammation and Immune Dysregulation in Pediatric Brain Tumors.","authors":"Rajanya Roy, Kornelius Kerl","doi":"10.1093/neuonc/noag168","DOIUrl":"https://doi.org/10.1093/neuonc/noag168","url":null,"abstract":"<p><p>Pediatric brain tumors (PBTs) remain a leading cause of cancer-related mortality in children, underscoring the need for more effective therapeutic strategies. These tumors arise from disrupted neurodevelopmental programs and evolve within a developmentally constrained immune landscape that is tolerogenic, epigenetically plastic, and susceptible to tumor-mediated co-option. Increasing evidence indicates that, besides molecular heterogeneity, the tumor immune microenvironment critically influences clinical outcomes. Despite its therapeutic promise, immunotherapy has yet to demonstrate consistent clinical benefit in most PBTs, highlighting the need for rational multimodal strategies guided by deeper understanding of tumor-immune interactions in the developing brain. To provide a comprehensive perspective on fetal immune ontogeny and its tumor-driven dysregulation we used medulloblastoma, pediatric gliomas, atypical teratoid/rhabdoid tumors, and ependymoma as representative entities. Drawing on insights from developmental neurobiology, tumor immunology, and emerging multi-omic studies, we outline how PBTs exploit physiological immune maturation programs to establish immune evasion, sustain chronic inflammation, and promote therapy resistance. We further discuss emerging multimodal immunotherapeutic strategies and next-generation CAR T-cell approaches currently under clinical investigation. In addition, we highlight therapeutic avenues such as targeting tumor-associated myeloid populations and key inflammatory regulators that may offer promising opportunities for future clinical translation. We believe this Review will help address current limitations in preclinical models, improve patient stratification and guide rational design of therapeutic strategies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183376","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":"AI in Neuro-Oncology: An Overarching Review.","authors":"Carla Pitarch-Abaigar, Philipp Lohmann, Patrick Aloy, Fatima Al-Shahrour, Omar Arnaout, Wenya Linda Bi, Norbert Galldiks, Jason T Huse, Philipp Karschnia, MacLean P Nasrallah, Areeba Patel, Rifaquat Rahman, Felix Sahm, Timothy R Smith, Joerg-Christian Tonn, Renato Umeton, Manuel Valiente, Mark Zarella, Raymond Y Huang, Spyridon Bakas","doi":"10.1093/neuonc/noag257","DOIUrl":"https://doi.org/10.1093/neuonc/noag257","url":null,"abstract":"<p><p>Artificial intelligence (AI) is increasingly being applied across neuro-oncology domains to analyze complex, high-dimensional, multimodal data. Despite major advances in the biological understanding and classification of CNS tumors, clinical outcomes for many of them remain poor, reflecting intra- and inter-tumor heterogeneity and limitations of conventional reductionist approaches. AI offers a paradigm shift to capture this heterogeneity and provide quantitative, reproducible diagnostic, predictive, and prognostic insights. This article describes a joint effort across the Response Assessment in Neuro-Oncology (RANO) working groups to provide an overarching review of the AI use across six key domains of neuro-oncology: neuroimaging, neuropathology, laboratory medicine, neurosurgery, drug discovery, and clinical trials. Applications closest to clinical use include imaging segmentation and quantification, AI-assisted image reconstruction, DNA methylation-based classification, and workflow optimization. Radiogenomics, WSI-based molecular prediction, AI-guided surgical targeting, liquid biopsy interpretation, AI-guided drug discovery, digital twins, and in silico trials remain promising but require stronger prospective validation. Key challenges include limited availability of large diverse datasets, variability in data acquisition and reference standards, and limited external validation. This review provides a unifying framework for understanding the role of AI across neuro-oncology and highlights key considerations for its responsible implementation, emphasizing standardization, reproducibility, multi-institutional validation, and human oversight.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183414","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":"Globalising the access to advanced molecular diagnostics of CNS tumors: Experience of the Molecular Neuro-Pathology (MNP) Outreach Consortium.","authors":"Olfat Ahmad, Felipe D'Almeida Costa, Wouter R L Hendrickx, Ahmed Gilani, Vaishali Suri, Nabe Al-Hasnawi, Monique Stenzel, Martin Lablans, Syed Ather Enam, Shahenda El-Naggar, Horacio Martinetto, Gustavo Sevlever, Blanca Diez, Maysa Al-Hussaini, Sith Sathornsumetee, Thidathip Wongsurawat, Ludi Dhyani Rahmartani, Naureen Mushtaq, Erdener Ozer, Christophe M Raynaud, Paromita Roy, Sushant S Vinarkar, Rimpa Basu Achari, Pablo Zoroquiain, Roger Gejman, Cristovam Scapulatempo Neto, Leslie D Kulikowski, João Victor Alves de Castro, Luiz Gustavo Dufner-Almeida, Beatriz Wolff, Yuri Reis Casal, Khurram Minhas, Andréa Maria Cappellano, Stefan Hamelmann, Mohamed S Abdelbaki, Lorena V Baroni, Abrar Al-Masamreh, Abdlrahman Eswed, Ute Bartels, Dominik Sturm, Martin Sill, David T W Jones, Areeba Patel, Felix Sahm, Stefan M Pfister","doi":"10.1093/neuonc/noag077","DOIUrl":"https://doi.org/10.1093/neuonc/noag077","url":null,"abstract":"<p><p>Central nervous system (CNS) tumors pose a major global health challenge, particularly in low- and middle-income countries (LMICs), where outcomes remain disproportionately poor. The global CONCORD-3 study (Lancet Oncology) highlighted stark disparities in five-year survival (2010-2014): from ∼15% in Thailand to 46% in Japan among adults, and from ∼ 80% in Denmark to < 40% in Brazil among children. Limited access to specialized pathology and molecular diagnostics in LMICs results in diagnostic uncertainty and restricted treatment options. DNA methylation-based tumor classification, has revolutionized CNS tumor diagnosis and got incorporated into the 2021 world health organization (WHO) CNS5 classification. However, its accessibility, feasibility, and performance in LMICs remain insufficiently explored. Importantly, several ethnic groups common in LMICs are underrepresented in current reference datasets. To address this, the Molecular Neuro-Pathology (MNP) Outreach Consortium was launched in Heidelberg, partnering with 11 countries-including nine LMICs from Asia, Africa, and South America. Early insights from Brazil, Jordan and Argentina, show methylation profiling changing diagnosis in up to 25% cases. Gains are greatest in pediatric and adolescents and young adults (AYA) populations. In addition, it reduced the designation of not otherwise specified (NOS) from 51.3% to 8.8% across 476 CNS tumours in Brazil.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170194","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":"A Multi-Omic Phenobank Reveals Axes of Glioblastoma Growth, Invasion, and Therapeutic Vulnerability.","authors":"Cecilia Krona, Soumi Kundu, Emil Rosen, Filippa Kruse, Madeleine Skeppås, Haris Babačić, Ida Larsson, Ludmila Elfineh, Maya Jeje Schuan Lü, Maria Escriva Conde, Ramy Elgendy, Zankruti Dave, Milena Doroszko, Katrin Rut-Halldorsdottir, Xiaofang Cao, Rashmi Ramachandra, Karl Holmberg Olausson, Mats Nilsson, Joachim Weischenfeldt, Johan Wikström, Maria Pernemalm, Anders Sundström, Irem Uppman, Hitesh Bhagavanbhai Mangukiya, Sven Nelander","doi":"10.1093/neuonc/noag255","DOIUrl":"https://doi.org/10.1093/neuonc/noag255","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) invasion is clinically decisive but difficult to model systematically. Existing patient-derived xenograft (PDX) resources rarely couple reproducible in vivo invasion phenotypes with matched multi-omic profiles at scale, limiting mechanistic insight and phenotype-informed therapeutic hypotheses.</p><p><strong>Methods: </strong>We established the HGCC Phenobank, comprising 65 patient-derived GBM stem-like cultures with matched multi-omic profiling and orthotopic engraftment in 449 mice. Blinded histopathology quantified ten invasion traits per case. These phenotypes were integrated with RNA sequencing, DNA methylation, and mass-spectrometry-based proteomics. Multi-Omic Factor Analysis (MOFA) identified latent molecular programs. Phenotype-specific RNA signatures were matched to LINCS drug-perturbation profiles and validated in 3D gliomasphere and ex vivo brain-slice assays.</p><p><strong>Results: </strong>Two dominant, reproducible invasion modes emerged across models: diffuse parenchymal infiltration and perivascular/condensed growth. Proneural cultures formed more aggressive tumors in immunodeficient mice, and mouse survival showed a modest correlation with patient survival in matched cases (Pearson r=0.1832, p=0.045). MOFA identified 15 latent factors; Factor 1, marked by ASCL1/OLIG1/OLIG2 programs across multiple molecular layers, was associated with increased tumor formation and diffuse invasion in mice. Higher Factor 1 scores were associated with significantly longer postoperative survival in both the matched patient cohort (p = 0.00018) and TCGA (p = 0.017), although Factor 1 was not associated with survival of the xenografted mice. Drug-signature matching separated mechanisms targeting diffuse versus perivascular invasion. Experimental validation confirmed phenotype-selective sensitivities, and inhibitors PIK-75 and buparlisib suppressed invasion dynamics across representative models in 3D and brain-slice assays.</p><p><strong>Conclusions: </strong>The HGCC Phenobank provides the first openly available PDX resource that systematically links GBM invasion phenotypes to multi-omic programs and therapeutic predictions. This framework enables reproducible model selection, mechanistic dissection of invasion modes, and phenotype-guided therapeutic discovery.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166768","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":"Clinical trial designs in the era of biomarker-guided therapies.","authors":"Julien Rousseau, Martin J Van den Bent, Patrick Y Wen","doi":"10.1093/neuonc/noag004","DOIUrl":"https://doi.org/10.1093/neuonc/noag004","url":null,"abstract":"<p><p>As molecular profiling improves, treatment responses are increasingly observed in smaller, biomarker-defined subgroups, highlighting the need for novel clinical trial designs and endpoints. We review principles for the selection and assessment of biomarkers, a crucial component of biomarker-enriched protocols, and illustrate common pitfalls in biomarker ascertainment through recent examples. We summarize current response assessment criteria and their integration into single-arm trials with surrogate endpoints based on response rate, which have supported recent accelerated regulatory approvals in biomarker-selected populations. We describe how window-of-opportunity trials can help validate CNS penetration and target engagement early, and define master protocol designs: basket, umbrella, and adaptive platform trials. Finally, we evaluate external control arms and their current role in neuro-oncology research. Throughout, we provide guidance on the use of novel designs and endpoints while preserving scientific rigor.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167466","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":"Fine-tuning the beam: Biomarker-guided radiation strategies in the evolving management of isocitrate dehydrogenase (IDH)-mutant glioma.","authors":"Ariel E Marciscano, Helen A Shih, Maximilian Niyazi","doi":"10.1093/neuonc/noag169","DOIUrl":"https://doi.org/10.1093/neuonc/noag169","url":null,"abstract":"<p><p>Sequential chemoradiotherapy remains a standard treatment option for patients with isocitrate dehydrogenase (IDH)-mutant gliomas. The results of the phase III INDIGO trial have led to the recent regulatory approval of vorasidenib, a brain-penetrant IDH1 and IDH2 inhibitor, indicated for patients with IDH1- or IDH2-mutant WHO grade 2 astrocytoma or oligodendroglioma after biopsy or resection. While IDH inhibitors represent a significant advancement for patients with IDH-mutant glioma, there is substantial controversy regarding which patients are most likely to derive benefit from IDH inhibition and how this strategy can be optimally integrated into clinical practice. Specifically, whether IDH inhibitors should be used prior to, in conjunction with or potentially in lieu of radiation-based treatment strategies are fundamental questions for the neuro-oncology community. Additionally, whether IDH inhibitors can be extrapolated to higher-grade disease settings or utilized in higher-risk patient populations remains unknown. These open questions provide an opportunity for the field of radiation oncology to develop pragmatic biomarker-based approaches to guide patient selection, to monitor treatment response and to identify optimal treatment strategy and timing/sequencing of treatment. Several candidate biomarkers have emerged for IDH-mutant glioma with unique potential to be rationally integrated into radiation oncology workflows to personalize care.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167548","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":"Spatial transcriptomics elucidates trajectories associated with transformation in malignant peripheral nerve sheath tumors.","authors":"Kanish Mirchia, Abhishek Bhattacharya, Jonas Krag Viken, Grant Eilers, Sixuan Pan, Iowis Zhu, Daniel Zhang, Ayesha Siddika, Varun Monga, Rosanna Wustrack, Brian S Na, Iain Carmichael, Joanna J Phillips, Line Jacques, Arie Perry, Calixto-Hope G Lucas, Melike Pekmezci, Harish N Vasudevan","doi":"10.1093/neuonc/noag251","DOIUrl":"https://doi.org/10.1093/neuonc/noag251","url":null,"abstract":"<p><strong>Background: </strong>Tumor invasion and malignant transformation are spatiotemporally coordinated processes that shape clinical behavior, diagnostic classification, and treatment response. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors that can arise sporadically or in people with neurofibromatosis type 1 (NF-1) yet how distinct spatial niches underlie MPNST intra-tumor heterogeneity, local invasion or malignant transformation from benign precursors are not fully understood.</p><p><strong>Methods: </strong>We integrate spatial analysis of 50,896 transcriptomes from 15 human MPNSTs with deep learning image analysis to define the interplay between genetic alterations, the immune microenvironment, and epigenetic cell fate regulation in MPNST invasion and transformation.</p><p><strong>Results: </strong>Spatial transcriptomics reveal distinct infiltrating immune cells and immunomodulatory spatial clusters in sporadic compared to NF-1 associated MPNSTs. Local invasion is marked by spatially defined immunomodulatory and dedifferentiation programs. Analysis of two NF-1 associated MPNSTs with contiguous morphologically defined neurofibroma and MPNST components demonstrates NF-1 associated tumors identified a similar malignant transformation process associated with dynamic immune infiltration, chromosome 9p loss, and dedifferentiation concomitant with increased cell proliferation. Finally, deep learning morphology encoders were trained on spatial transcriptomic data to predict spatial transcriptomic cluster identity and chromosome 9p loss from hematoxylin and eosin stained (H&E) images although the generalizability of such encoders remains a challenge.</p><p><strong>Conclusions: </strong>Our data provide a spatial framework for peripheral nerve sheath tumor transformation although the limited sample size of the present cohort will require additional validation of the proposed model.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171074","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":"A Dual Role for SIRPα in Triple-Negative Breast Cancer Brain Metastasis.","authors":"Roberto H Barbier, Matthew S Waitkus","doi":"10.1093/neuonc/noag243","DOIUrl":"https://doi.org/10.1093/neuonc/noag243","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167963","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":"Fanconi anemia pathway disruption drives lomustine sensitivity in glioma.","authors":"Hannes Becker, Bianca Walter, Lara Annina Haeusser, Jil Trampert, Marcello Zago, Surender Surender, Louise Maise, Polina Volos, Sarah Erdmann, Laurence Kuhlburger, Aaron Falkner, Foteini Tsiami, Lorenz Dörner, Marko Maric, Albert Skotnicki, Hannes Jägle, Dimas Echeverria, Samual Jackson, Ansh Tripathi, Xavier Segarra-Visent, Anushka Bhandari, Susanne Beck, Marcos Tatagiba, Sven Nahnsen, Manfred Claassen, Reka Haraszti, Frank Szulzewsky, Eric C Holland, Daniel Josef Merk, Ghazaleh Tabatabai","doi":"10.1093/neuonc/noag254","DOIUrl":"https://doi.org/10.1093/neuonc/noag254","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic options for progressive glioblastoma remain limited, with chlorethyl-cyclohexyl-nitrosourea (CCNU, lomustine) among the approved treatments. Beyond MGMT gene promoter methylation, molecular determinants of CCNU sensitivity or resistance are ill- defined.</p><p><strong>Methods: </strong>We employed genome-wide functional knockout screening using the CRISPR-Cas9 technology to identify and subsequently validate modulators of response to CCNU in experimental glioma. We established an immunocompetent glioma mouse model to enable functional interrogation of Fanconi anemia pathway (FA) genes in tumor growth and synthetic lethal interactions in vivo using the RCAS/tv-a somatic gene delivery system.</p><p><strong>Results: </strong>Multiple FA pathway members recurrently emerged as potent synthetic lethal interactors of CCNU treatment. In vivo knockdown of Fancm accelerated tumor onset and significantly increased CCNU sensitivity. Consistently, FA pathway inhibition enhanced CCNU efficacy across in vitro, ex vivo and in vivo models.</p><p><strong>Conclusion: </strong>Together, these findings identify FA pathway components as key synthetic lethal interactors of CCNU response and reveal a therapeutically actionable vulnerability in glioblastoma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170402","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}