Neuro-oncologyPub Date : 2025-10-21DOI: 10.1093/neuonc/noaf245
Adrian B Levine, Julie Bennett, Prabhumallikarjun Patil, Ian Burns, Robert Siddaway, Cyril Li, Joseline Haizel-Cobbina, Mansuba Rana, Richard Yuditskiy, Andrew Son, Yoshiko Nakano, Palak Patel, I-Chen Ho, Michelle Ku, Alexander T Lyons, José E Velázquez Vega, Matthew J Schniederjan, Craig Erker, Chantel Cacciotti, Mariarita Santi, Ernest J Nelson, Sylvia Cheng, Christopher Dunham, Bev Wilson, Karina Black, Frank Van Landeghem, Liana Nobre, David D Eisenstat, Ana S Guerreiro Stücklin, Annette Weiser, Valerie Larouche, Panagiota Giannakouros, Adriana Fonseca, Lane Williamson, Igor L Fernandes, Ashley S Plant-Fox, Adam Fleming, Shawde Campbell, Naureen Mushtaq, Syed Ibrahim Bukhari, Khurram Minhas, Richard T Graham, Scott Raskin, Filip Jadrijevic-Cvrlje, Louise Ludlow, Mary V Macneil, Jean M Mulcahy-Levy, Samantha Demarsh, Kohei Fukuoka, Kai Yamasaki, Tomonari Suzuki, Fumiharu Ohka, Atsufumi Kawamura, Yoshiki Arakawa, Takashi Ishihara, Fumiyuki Yamasaki, Jordan R Hansford, Amanda Luck, Maclean P Nasrallah, Helen Toledano, Roaya M Masoud, Alvaro Lassaletta, Luis Blasco-Santana, John-Paul Kilday, Alisa Talianski, Caroline Davies, James Johnston, Andrew T Hale, Peter B Dirks, James T Rutka, Michael C Dewan, Uri Tabori, Cynthia E Hawkins
{"title":"Integrated clinical and molecular landscape of disseminated pediatric low-grade glioma.","authors":"Adrian B Levine, Julie Bennett, Prabhumallikarjun Patil, Ian Burns, Robert Siddaway, Cyril Li, Joseline Haizel-Cobbina, Mansuba Rana, Richard Yuditskiy, Andrew Son, Yoshiko Nakano, Palak Patel, I-Chen Ho, Michelle Ku, Alexander T Lyons, José E Velázquez Vega, Matthew J Schniederjan, Craig Erker, Chantel Cacciotti, Mariarita Santi, Ernest J Nelson, Sylvia Cheng, Christopher Dunham, Bev Wilson, Karina Black, Frank Van Landeghem, Liana Nobre, David D Eisenstat, Ana S Guerreiro Stücklin, Annette Weiser, Valerie Larouche, Panagiota Giannakouros, Adriana Fonseca, Lane Williamson, Igor L Fernandes, Ashley S Plant-Fox, Adam Fleming, Shawde Campbell, Naureen Mushtaq, Syed Ibrahim Bukhari, Khurram Minhas, Richard T Graham, Scott Raskin, Filip Jadrijevic-Cvrlje, Louise Ludlow, Mary V Macneil, Jean M Mulcahy-Levy, Samantha Demarsh, Kohei Fukuoka, Kai Yamasaki, Tomonari Suzuki, Fumiharu Ohka, Atsufumi Kawamura, Yoshiki Arakawa, Takashi Ishihara, Fumiyuki Yamasaki, Jordan R Hansford, Amanda Luck, Maclean P Nasrallah, Helen Toledano, Roaya M Masoud, Alvaro Lassaletta, Luis Blasco-Santana, John-Paul Kilday, Alisa Talianski, Caroline Davies, James Johnston, Andrew T Hale, Peter B Dirks, James T Rutka, Michael C Dewan, Uri Tabori, Cynthia E Hawkins","doi":"10.1093/neuonc/noaf245","DOIUrl":"https://doi.org/10.1093/neuonc/noaf245","url":null,"abstract":"<p><strong>Background: </strong>Pediatric-type low-grade gliomas (PLGG) are the most common central nervous system (CNS) tumor in children. Many are indolent and have excellent outcomes, however some inexplicably spread throughout the CNS leading to increased morbidity and mortality.</p><p><strong>Methods: </strong>To better understand this rare and difficult-to-treat entity, as well as the features associated with dissemination in CNS tumors, we assembled a large international cohort (n = 269) of patients with disseminated PLGG with detailed clinical and molecular characterization, including DNA sequencing and methylome profiling.</p><p><strong>Results: </strong>We identified three subgroups of patients based on the temporal and spatial distribution of dissemination. Tumors with diffuse leptomeningeal spread without a primary tumor mass and those occurring in infants had the worst clinical outcomes. The genetics overlapped substantially with that of non-disseminated PLGG, suggesting that non-genetic mechanisms are an important contributor to dissemination. Therapeutically, targeted RAS/MAPK-pathway inhibition was more effective than conventional chemotherapy as first or second-line treatment.</p><p><strong>Conclusion: </strong>In sum, this cohort increases our clinical and biological understanding of this rare disease, provides insights for improving patient care, and directs future clinical trials and basic science research.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337379","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}
Neuro-oncologyPub Date : 2025-10-17DOI: 10.1093/neuonc/noaf236
Rosa Luning, Pim J French, Wouter J F Vanbilloen, Lisa Dobber, Levi Van Hijfte, Raoull Hoogendijk, Martin J Van Den Bent, Reno Debets, Marjolein Geurts
{"title":"T cell immunity in glioma and potential implications for immunotherapy: a systematic review.","authors":"Rosa Luning, Pim J French, Wouter J F Vanbilloen, Lisa Dobber, Levi Van Hijfte, Raoull Hoogendijk, Martin J Van Den Bent, Reno Debets, Marjolein Geurts","doi":"10.1093/neuonc/noaf236","DOIUrl":"https://doi.org/10.1093/neuonc/noaf236","url":null,"abstract":"<p><strong>Background: </strong>T cell-based immunotherapies have had limited success in glioma thus far. Here, we evaluate the literature on abundance, spatial distribution and phenotypical characteristics of T cells in the tumor micro-environment (TME) of IDH-mutant and IDH-wildtype glioma, with the aim to understand how these measures relate to immunotherapy resistance and to aid the development of immunotherapies for glioma.</p><p><strong>Methods: </strong>Medline, Embase, Web of Science Core Collection, Google Scholar and the Cochrane Central Register of Controlled Trials were systematically searched up to May 6th, 2025. Out of 4,303 articles screened, 85 studies examining T cell immunity in human glioma were selected. We collected information about tumor subtype, grade, methods, T cell abundance, spatial distribution, phenotypes and prognostic significance.</p><p><strong>Results: </strong>T cells are present in the glioma TME, but at heterogeneous and generally low densities, especially in IDH-mutant glioma. T cell abundance increases with higher WHO grade and upon recurrence. T cells cluster around blood vessels, especially in IDH-mutant glioma. Glioma-infiltrating T cells largely display a late-differentiated phenotype (CD45RA-CCR7-C62L-), expressing markers that signify sustained antigen activation and exhaustion (PD-1, CTLA-4, TIM-3, LAG-3, CD39 and TIGIT). This phenotype coincides with decreased anti-tumor cytotoxicity and is spatially enriched in the myeloid-rich, hypoxic tumor core. Prognostic significance remains controversial.</p><p><strong>Conclusions: </strong>T cells in glioma are scarce, generally fully differentiated and functionally inert. Understanding and reinvigorating the deficient T cell response will be essential for successful immunotherapies. Future research should incorporate functional and spatial immune profiling to optimize and personalize immunotherapeutic strategies for glioma patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308671","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}
Neuro-oncologyPub Date : 2025-10-16DOI: 10.1093/neuonc/noaf246
David Schiff, Xiaobu Ye, Jing Li, Benjamin M Ellingson, Patrick Y Wen, Tobias Walbert, Jian Campian, L Burt Nabors, Byram H Ozer, Arati Desai, Antonio Omuro, Serena Desideri, Neeraja Danda, Stuart Grossman, Ranjit S Bindra
{"title":"Phase I/II and Window-of-Opportunity Study of Pamiparib and Metronomic Temozolomide for Recurrent IDH Mutant Gliomas.","authors":"David Schiff, Xiaobu Ye, Jing Li, Benjamin M Ellingson, Patrick Y Wen, Tobias Walbert, Jian Campian, L Burt Nabors, Byram H Ozer, Arati Desai, Antonio Omuro, Serena Desideri, Neeraja Danda, Stuart Grossman, Ranjit S Bindra","doi":"10.1093/neuonc/noaf246","DOIUrl":"https://doi.org/10.1093/neuonc/noaf246","url":null,"abstract":"<p><strong>Background: </strong>Preclinical studies demonstrate activity of PARP inhibitors in IDH mutant gliomas. We investigated safety, tolerability, pharmacokinetics, and efficacy of the PARP inhibitor pamiparib in conjunction with metronomic low-dose temozolomide in patients with recurrent IDH mutant (IDHmt) gliomas in a multicenter Phase I/II/window of opportunity study.</p><p><strong>Methods: </strong>Patients received pamiparib in conjunction with daily temozolomide. Following Phase I determination of MTD, we enrolled two patient cohorts (Arm A, multiple prior chemotherapy regimens; Arm B, single prior regimen) in a two-stage design. Exploratory cohorts examined grade 4 IDHmt patients and intratumoral pharmacokinetics of pamiparib. The primary endpoint was objective radiographic response (ORR) by RANO criteria.</p><p><strong>Results: </strong>66 subjects were enrolled. We established pamiparib 60 mg twice daily with temozolomide 20 mg daily as the phase II dose. In non-enhancing and enhancing tumor, pamiparib exhibited an unbound tumor/plasma ratio of 0.92 and 0.98 respectively. 0/15 Arm A and 1/24 Arm B patients achieved a centrally confirmed partial response. Median progression-free survival for Arm A was 5.9 months (95% CI, 1.2-14.8 months), and for Arm B 9.7 months (95% CI, 5.7-21.7 months). Grade 3+ anemia and neutropenia affected 24% and 33% of patients respectively. Twenty-two of 66 patients (33.3%) discontinued study treatment for reasons other than tumor progression.</p><p><strong>Conclusion: </strong>Pamiparib appeared to achieve sufficient pharmacologically active concentrations in both enhancing and non-enhancing tumors. While some patients achieved prolonged progression-free survival, combination with temozolomide did not produce a meaningful ORR in IDHmt recurrent gliomas. Cumulative hematologic toxicity was substantial and impacted long-term tolerability.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302272","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}
Neuro-oncologyPub Date : 2025-10-16DOI: 10.1093/neuonc/noaf241
Mirela-Diana Ilie, Álvaro Flores-Martínez, Marie Chanal, Maxime Lepetit, Benoit Samson, Ayoub Lehiani, Alexandre Vasiljevic, Laura Chinezu, Emmanuel Jouanneau, David Bernard, Olivier Gandrillon, Franck Picard, Gérald Raverot, Philippe Bertolino
{"title":"Mast cells act as pro-angiogenic and pro-tumorigenic players in pituitary gonadotroph tumors.","authors":"Mirela-Diana Ilie, Álvaro Flores-Martínez, Marie Chanal, Maxime Lepetit, Benoit Samson, Ayoub Lehiani, Alexandre Vasiljevic, Laura Chinezu, Emmanuel Jouanneau, David Bernard, Olivier Gandrillon, Franck Picard, Gérald Raverot, Philippe Bertolino","doi":"10.1093/neuonc/noaf241","DOIUrl":"https://doi.org/10.1093/neuonc/noaf241","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME) represents a promising avenue to understand gonadotroph tumors and develop therapeutic tools. Here, we aimed to gain insight into the tumorigenesis mechanisms driven by the gonadotoph TME.</p><p><strong>Methods: </strong> Single-cell and spatial-omics were combined with histological analysis. Mice engrafted with tumor cells were used for functional validation.</p><p><strong>Results: </strong> using single-cell and spatial transcriptomic data from gonadotroph tumors and normal tissues, we identified mast cells in the microenvironment of gonadotroph tumors and confirmed their physical and functional interaction with endothelial cells. Quantification of mast cells in 40 patients suggested their pro-tumoral role as tumors relapsing after surgery harbored more mast cells. More interestingly, the distribution of mast cells was associated with the presence of a higher number of blood vessels, with an increased microvessel density (MVD), and with blood vessels with thicker walls. Ligand-receptor network analysis highlighted VEGFA as a modulator of mast/endothelial cell communication, a result confirmed by the identification of intratumoral mast cells expressing VEGFA in mouse and human gonadotroph tumors. Finally, using mice engrafted with gonadotroph tumor cells, we demonstrated that the depletion of mast cells reduces tumor volume through increased apoptosis. These observations were associated with increased hemorrhagic areas and a significant reduction of the number of blood vessels and MVD as evidenced in human gonadotroph tumors.</p><p><strong>Conclusion: </strong> we demonstrate that mast cells represent a new actor of the gonadotroph TME, and highlight their pro-angiogenic and pro-tumorigenic roles as potential targets for the therapeutic treatment of gonadotroph tumors.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302149","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}
Neuro-oncologyPub Date : 2025-10-15DOI: 10.1093/neuonc/noaf244
Floris P Barthel
{"title":"Uncommon Territory: The Clinical and Molecular Profile of Metastatic Gliomas.","authors":"Floris P Barthel","doi":"10.1093/neuonc/noaf244","DOIUrl":"https://doi.org/10.1093/neuonc/noaf244","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302267","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}
Neuro-oncologyPub Date : 2025-10-15DOI: 10.1093/neuonc/noaf232
Jason T Huse
{"title":"Advancing intraoperative diagnostics, one (or rather three) mutations at a time.","authors":"Jason T Huse","doi":"10.1093/neuonc/noaf232","DOIUrl":"https://doi.org/10.1093/neuonc/noaf232","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302116","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}
Neuro-oncologyPub Date : 2025-10-14DOI: 10.1093/neuonc/noaf108
Ogechukwu A Asogwa, Linda Dirven, Tobias Walbert, Terri S Armstrong, David Arons, Martin J van den Bent, Jaishri Blakeley, Marijke B Coomans, Paul D Brown, Helen Bulbeck, Susan M Chang, Corneel Coens, Mark R Gilbert, Robin Grant, Rakesh Jalali, Johan A F Koekkoek, Pankaj Kumar Panda, Danielle Leach, Heather Leeper, Tito Mendoza, Lakshmi Nayak, Kathy Oliver, Jaap C Reijneveld, Emilie Le Rhun, Larry Rubinstein, Jennie W Taylor, Michael Weller, Patrick Y Wen, Martin J B Taphoorn
{"title":"Establishing the content validity of patient-reported outcome measures used in neuro-oncology based on the WHO ICF framework: Part of the RANO-PRO initiative.","authors":"Ogechukwu A Asogwa, Linda Dirven, Tobias Walbert, Terri S Armstrong, David Arons, Martin J van den Bent, Jaishri Blakeley, Marijke B Coomans, Paul D Brown, Helen Bulbeck, Susan M Chang, Corneel Coens, Mark R Gilbert, Robin Grant, Rakesh Jalali, Johan A F Koekkoek, Pankaj Kumar Panda, Danielle Leach, Heather Leeper, Tito Mendoza, Lakshmi Nayak, Kathy Oliver, Jaap C Reijneveld, Emilie Le Rhun, Larry Rubinstein, Jennie W Taylor, Michael Weller, Patrick Y Wen, Martin J B Taphoorn","doi":"10.1093/neuonc/noaf108","DOIUrl":"10.1093/neuonc/noaf108","url":null,"abstract":"<p><strong>Background: </strong>Instruments to assess patient-reported outcomes (PRO) should generate high-quality evidence. Reliable PRO evidence is essential to policymakers, in conjunction with outcomes such as survival and radiological response, to understand the net clinical benefit of antitumor treatments. This study aimed to establish the content validity of 215 identified PRO measures used in patients with brain tumors.</p><p><strong>Methods: </strong>A survey (n = 148 items) was developed reflecting aspects of the WHO International Classification of Functioning, Disability, and Health (ICF) framework. Patients with brain tumors, their proxies, and healthcare professionals (HCPs) were asked to rate each survey item on relevance. An item was considered a relevant issue if ≥25% of the patients or proxies or ≥50% of the HCPs considered that item to be an issue. Next, all items in the identified PRO measures were linked to ICF and relevant items in the survey, and the percentage of content coverage was calculated.</p><p><strong>Results: </strong>In total, 114 patients, 71 proxies, and 65 HCPs from different countries completed the survey. Fifty-six of 148 (37.8%) items in the survey were considered relevant. The most important aspects mentioned by both patients and proxies were difficulty concentrating, difficulty remembering, multitasking, and handling stress. Depending on the definition, between 35% and 49% of PRO measures were considered to have sufficient content validity (≥80% coverage).</p><p><strong>Conclusion: </strong>The content validity was insufficient in more than half of the identified PRO measures, particularly multidimensional measures. Future research should investigate whether different approaches to PRO assessment better meet the needs of all stakeholders.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2399-2414"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapy-induced senescent glioblastoma cells sustain a procancer immune microenvironment by activating DDX58-mediated STAT1 signaling.","authors":"Zhixing Wang, Yuxin Zhang, Fan Wu, Bojun Qiu, Yiyun Yin, Xinrun Wang, Ruoyu Huang, Xin Zhang, Zhiyan Sun, Wanjun Tang, Zefan Jing, Wei Han, Tao Jiang, Xiaozhong Peng","doi":"10.1093/neuonc/noaf107","DOIUrl":"10.1093/neuonc/noaf107","url":null,"abstract":"<p><strong>Background: </strong>Depending on the context, therapy-induced cancer cell senescence promotes or inhibits tumor progression and recurrence, but the underlying mechanism and effects on the tumor immune microenvironment are poorly understood.</p><p><strong>Methods: </strong>Here, we developed senescent glioblastoma cell models in vitro via drug treatment. The protumor function of senescent cells was demonstrated by coinjection of chemotherapy-induced senescent cells with tumorigenic GL261 cells in C57BL/6J male mice. In addition, conditioned medium coculture experiments were used to explore the functions of senescent glioblastoma cells in vitro. Mechanistically, through a CRISPR-Cas9-based screen, we revealed that the RNA-binding protein DDX58 was induced in senescent glioblastoma cells. By combining RNA sequencing and protein mass spectrometry analysis, we observed that STAT1 signaling was activated. Immunoprecipitation experiments were subsequently performed to identify the interaction between DDX58 and STAT1.</p><p><strong>Results: </strong>We show that glioblastoma cells can enter a senescent state after chemotherapy. In vivo, senescent glioblastoma cells have a tumor-promoting function and reduce survival in male mice. Mechanistically, we found that the RNA-binding protein DDX58 plays an important role in therapy-induced senescent glioblastoma. Inhibition of DDX58 slowed therapy-induced senescence. The activation of DDX58 depends on the accumulation of mitochondrial double-stranded RNA (mtdsRNA) in the cytoplasm via the BAX protein. Moreover, DDX58 promotes the recruitment of tumor-associated macrophages (TAMs) and their M2-like polarization by activating the STAT1-mediated transcription of colony-stimulating factor 1 (CSF1). We also revealed that DDX58 regulates STAT1 at the post-translational level by inhibiting the ubiquitin E3 ligase TRIM21-mediated STAT1 ubiquitination. Compared with temozolomide (TMZ) treatment alone, treatment with fludarabine, which blocks STAT1 signaling, combined with TMZ can more effectively reduce the recruitment of TAMs and delay tumor growth in vivo. Moreover, knockdown of STAT1 enhances the therapeutic effect of TMZ in vivo and prolongs the survival of tumor-bearing male mice.</p><p><strong>Conclusion: </strong>A critical mechanism for the protumor immune microenvironment mediated by therapy-induced senescent glioblastoma cells, the DDX58-STAT1-CSF1 axis, may be a potential therapeutic avenue for alleviating traditional therapy-induced glioblastoma cell senescence.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2265-2280"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuro-oncologyPub Date : 2025-10-14DOI: 10.1093/neuonc/noaf081
Cody L Nesvick, Liang Zhang, Yuqian Yan, Alexander Q Wixom, Feda H Hamdan, Jizhi Ge, Jacob B Anderson, Alexandre Gaspar-Maia, Steven A Johnsen, David J Daniels
{"title":"SWI/SNF complexes govern ontology-specific transcription factor function in MYC-subtype atypical teratoid rhabdoid tumor.","authors":"Cody L Nesvick, Liang Zhang, Yuqian Yan, Alexander Q Wixom, Feda H Hamdan, Jizhi Ge, Jacob B Anderson, Alexandre Gaspar-Maia, Steven A Johnsen, David J Daniels","doi":"10.1093/neuonc/noaf081","DOIUrl":"10.1093/neuonc/noaf081","url":null,"abstract":"<p><strong>Background: </strong>Atypical teratoid rhabdoid tumor (ATRT) is a deadly central nervous system embryonal tumor caused by loss of SMARCB1, a core subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes. SMARCB1-deficient cancers are defined by loss of cell differentiation-associated enhancers, but how SWI/SNF interacts with other arbiters of cell differentiation (specifically lineage-specific transcription factors [TFs]) remains poorly understood.</p><p><strong>Methods: </strong>We leveraged a multi-omics approach, patient-derived ATRT cells, and patient-derived orthotopic xenografts to investigate the interplay of SWI/SNF with lineage-specific TFs in a clinically relevant setting.</p><p><strong>Results: </strong>We observe that an activating protein 1 (AP-1)-dependent transcriptional regulatory network is lost in ATRT, and AP-1 and lineage-specific TFs TEAD1 and ZIC2 require SMARCB1 for enhancer binding. SMARCB1-dependent SWI/SNF integrates transcriptional functions of lineage-specific TFs into a core regulatory circuit that depends on the AP-1 subunit c-JUN, whose expression is determined by a SMARCB1-dependent super-enhancer that is lost in ATRT-MYC. In the absence of SMARCB1, lineage-specific TFs are sequestered to promoters, where they maintain core transcriptional programs necessary for cell survival. Targeting residual, promoter-proximal TF activity by a protein degrader of the SWI/SNF ATPase SMARCA4 or small-molecule inhibitors that indirectly inhibit AP-1 and TEAD activity abrogates expression of these networks, reducing cell viability in vitro and prolonging survival in an orthotopic patient-derived xenograft model.</p><p><strong>Conclusions: </strong>These results demonstrate SWI/SNF complexes are critical for lineage-specific TF binding and activity at both promoters and enhancers. In the context of ATRT, these findings reveal a previously underappreciated therapeutic vulnerability in targeting residual promoter-proximal TF function in ATRT.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2445-2460"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuro-oncologyPub Date : 2025-10-14DOI: 10.1093/neuonc/noaf118
Martin J van den Bent, Michael A Vogelbaum, Tim Cloughesy, Norbert Galldiks, Nathalie L Albert, Joerg-Christian Tonn, Edward Avila, Jason Fangusaro, David Mirsky, Arjun Sahgal, Ricardo Soffietti, Philipp Karschnia, Minesh Mehta, Michelle M Kim, Florien Boele, Jason T Huse, Lakshmi Nayak, Mary Jane Lim-Fat, Emilie le Rhun, Annick Desjardins, Eudocia Q Lee, Ugonma Chukwueke, Johan A F Koekkoek, Tito Mendoza, Ashlee R Loughan, Joshua A Budhu, Spyridon Bakas, Raymond Y Huang, Javier E Villanueva-Meyer, Jose Pablo Leone, Hideho Okada, David A Reardon, Wenya L Bi, Patrick Y Wen, Susan M Chang
{"title":"Response Assessment in Neuro-Oncology (RANO) 2009-2025: Broad scope and implementation-A progress report.","authors":"Martin J van den Bent, Michael A Vogelbaum, Tim Cloughesy, Norbert Galldiks, Nathalie L Albert, Joerg-Christian Tonn, Edward Avila, Jason Fangusaro, David Mirsky, Arjun Sahgal, Ricardo Soffietti, Philipp Karschnia, Minesh Mehta, Michelle M Kim, Florien Boele, Jason T Huse, Lakshmi Nayak, Mary Jane Lim-Fat, Emilie le Rhun, Annick Desjardins, Eudocia Q Lee, Ugonma Chukwueke, Johan A F Koekkoek, Tito Mendoza, Ashlee R Loughan, Joshua A Budhu, Spyridon Bakas, Raymond Y Huang, Javier E Villanueva-Meyer, Jose Pablo Leone, Hideho Okada, David A Reardon, Wenya L Bi, Patrick Y Wen, Susan M Chang","doi":"10.1093/neuonc/noaf118","DOIUrl":"10.1093/neuonc/noaf118","url":null,"abstract":"<p><p>Since its first activities in 2008 and 2009, the Response Assessment in NeuroOncology (RANO) group has given guidance on response assessment, trial design, and trial procedures to improve and standardize the way clinical trials in neurooncological studies are performed. To achieve its objectives, a variety of working groups have been initiated that cover many aspects of clinical trial design and outcome assessment in patients with tumors affecting the Central Nervous System. The RANO working groups are built on expertise without a formal structure, which makes rapid responses to new developments possible. RANO is aiming at evidence-based guidelines and recommendations, but in the absence of evidence will provide consensus-based guidance achieved by inviting recognized international experts. In its 15 years of existence, more than 60 RANO papers have been published mostly in high-ranking journals, and its recommendations have been accepted by regulators and industry as guiding principles. RANO organizes two meetings per year, one in conjunction with the annual American Society for Clinical Oncology (ASCO) meeting, and one during the annual Society for Neuro-Oncology meeting. These meetings are open, as are the working groups of RANO. New initiatives are welcomed.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2209-2224"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}