Neuro-oncology最新文献

{"title":"Correlative studies in central nervous system tumors clinical trials: The emerging role of microbiome research.","authors":"Raoull Hoogendijk, Marjolein Geurts, Jasper van der Lugt","doi":"10.1093/neuonc/noaf111","DOIUrl":"10.1093/neuonc/noaf111","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2105-2106"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029906","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":"SOX2 commands LIM homeobox transcription factors in choroid plexus development and tumorigenesis.","authors":"Lukas J Faltings, Fengjuan Lin, Mariam Zahran, Heena Jalili, Anjali Siluveru, Mahek Chaudry, Leah M Wachsmuth, Navjot Guru, Melanie Schoof, Ping Cao, Yuan Huang, Noreen Mian, Sohyun Moon, Asmaa Zahran, Kristen Green, Siddhi Modi, Maheen Umer, James Q Virga, Ying-Tao Zhao, Ulrich Schüller, Qun Li, Haotian Zhao","doi":"10.1093/neuonc/noaf085","DOIUrl":"10.1093/neuonc/noaf085","url":null,"abstract":"<p><strong>Background: </strong>Choroid plexus (CP) tumors are rare brain neoplasms that mainly affect the pediatric population. Unlike benign CP papilloma (CPP), CP carcinoma (CPC) is an aggressive cancer with a dismal survival rate. Despite chromosome-wide rearrangements, drivers of most CP tumors remain elusive except recurrent alterations in TP53. Studies of signaling dysregulation may bring biological understanding of these malignancies. Previous studies implicated NOTCH signaling in CP tumors; we developed mouse models of CP tumors driven by NOTCH activation and Trp53 loss, respectively. This work examined the role of the transcription factor SOX2 in CP development and tumorigenesis.</p><p><strong>Methods: </strong>Multi-omics approaches were used to characterize cellular heterogeneity in NOTCH-driven CP tumors. SOX2 functions in the molecular signature of tumor cells were investigated.</p><p><strong>Results: </strong>Single-cell transcriptomics and epigenetics methods identified diverse cell populations in tumors that resemble normal CP, such as epithelial and glial groups. Pseudotime trajectory analysis indicated that NOTCH-driven CP tumor arises from bipotential glial progenitors and retains a progenitor-like signature characterized by an enhanced SOX2 profile. SOX2 inactivation attenuated progenitor-like features and blunted tumor growth. Integrative omics studies revealed SOX2 binding to genes expressed in progenitors in the rhombic lip, including LIM homeobox transcription factors LMX1A and LMX1B. Consistently, SOX2 maintains progenitor identity through regulating their expression in CP tumors and during development, whereas LMX1A and LMX1B support SOX2 functions in tumor cell proliferation. Furthermore, spatial transcriptomics revealed aberrant SOX2 and LMX1A expression in human CP tumors.</p><p><strong>Conclusions: </strong>SOX2-LMX1 signaling maintains progenitor identity in CP development and tumor formation.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2006-2022"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701122","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":"Gut microbiome modulates the outcome in primary central nervous system lymphoma patients undergoing chemotherapy: An ancillary study from the BLOCAGE trial.","authors":"Isaias Hernández-Verdin, Eva Kirasic, Karima Mokhtari, Noemie Barillot, Lucas Rincón de la Rosa, Elise Sourdeau, Yahse Abada, Magali Le Tarff-Tavernier, Lucia Nichelli, Laura Rozenblum, Aurélie Kas, Bertrand Mathon, Sylvain Choquet, Caroline Houillier, Khê Hoang-Xuan, Agusti Alentorn","doi":"10.1093/neuonc/noaf059","DOIUrl":"10.1093/neuonc/noaf059","url":null,"abstract":"<p><strong>Background: </strong>Primary central nervous system lymphoma (PCNSL) treatment relies on a high-dose methotrexate-based chemotherapy (HD-MTX-based CT) regimen; however, whether there is a specific microbiota composition association with treatment response and clinical outcomes remains incompletely understood.</p><p><strong>Methods: </strong>We conducted a prospective study of PCNSL patients, included in the clinical trial NCT02313389 and the ancillary study NCT04253496 from 2020 to 2023, where patients were treated with first-line HD-MTX-based polychemotherapy without a consolidation treatment. Stool (n = 52), cerebrospinal fluid (CSF, n = 52), and plasma samples (n = 35) were collected before and/or after therapy initiation to perform metagenomic, flow cytometry, and metabolomic analyses. Plasma metabolomic data of 90 patients also included in the BLOCAGE clinical trial was subsequently used as a validation cohort.</p><p><strong>Results: </strong>Unsupervised clustering of microbial data identified two distinct gut microbial communities, differing in Parabacteroides distasonis abundance, which correlated with progression-free survival and overall survival in both uni- and multivariate analyses. Higher P. distasonis levels were linked to increased plasma betaine-valine metabolites and enhanced CD8 T cell infiltration in the CSF, suggesting a connection between gut microbiota and immune regulation. Stratifying the validation cohort by betaine-valine content confirmed these clinical associations.</p><p><strong>Conclusions: </strong>Our findings suggest that gut microbiome communities modulate clinical outcomes in PCNSL patients undergoing standard treatment. Moreover, after future validation in external cohorts, the quantification of Parabacteroides distasonis could potentially provide a basis for patient stratification and guide personalized therapeutic strategies in the near future.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2090-2104"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573503","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":"S-palmitoylation of c-MET by CK2α-mediated zDHHC15 phosphorylation drives glioblastoma stem cell tumorigenicity.","authors":"Yang Wang, Zhengxin Chen, Rui Li, Dong Wei, Shuai Wang, Hui Luo, Yiming Tu, Cen Liu, Haibiao Xu, Jiachen Xu, Mingtian Ding, Minghui Meng, Tao Fu, Yangyin Ding, Jun Yin, Wei Wu, Jing Ji, Huibo Wang","doi":"10.1093/neuonc/noaf098","DOIUrl":"10.1093/neuonc/noaf098","url":null,"abstract":"<p><strong>Background: </strong>The c-MET signaling pathway is crucial for the self-renewal and tumorigenic capacity of cancer stem cells, including glioblastoma stem cells (GSCs). Despite its recognized importance, the precise mechanisms of c-MET activation in these cells remain elusive. This study aimed to elucidate the key regulatory elements and mechanisms governing c-MET function in GSCs.</p><p><strong>Methods: </strong>The mediation of S-palmitoylation and dimerization of c-MET by zDHHC15 was validated using metabolic labeling, acyl-PEG exchange (APE), BS3 crosslinking, and co-immunoprecipitation. The role of the CK2α-zDHHC15-c-MET axis in tumorigenesis, along with the antitumor efficacy of TVB-3166, was confirmed through cell proliferation, limiting dilution, and intracranial tumor growth assays.</p><p><strong>Results: </strong>We revealed that zDHHC15, a member of the DHHC family of palmitoyl acyltransferases, mediates the palmitoylation of c-MET at Cys801, which is critical for c-MET O-glycosylation, dimerization, and activation. We further identified a novel regulatory loop in which CK2α phosphorylates zDHHC15 at Tyr92, increasing its stability and c-MET binding, thereby enhancing c-MET palmitoylation. zDHHC15 was found to be specifically enriched in GSCs, and its targeted knockdown markedly impaired their self-renewal and tumorigenic capabilities both in vitro and in vivo. Therapeutically, we introduced TVB-3166, an inhibitor of c-MET S-palmitoylation, which demonstrated robust inhibitory effects on GSC growth in orthotopic xenograft models.</p><p><strong>Conclusions: </strong>This study establishes the CK2α-zDHHC15-c-MET axis as a pivotal regulatory hub in GSC maintenance and identifies c-MET S-palmitoylation as a novel and promising therapeutic target for the treatment of glioblastoma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1972-1986"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022978","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":"Targeting PDGFRA-SHP2 signaling enhances radiotherapy in IDH1-mutant glioma.","authors":"Xiaozhou Yu, Xiao Song, Deanna Tiek, Runxin Wu, Maya Walker, Craig Horbinski, Bo Hu, Shi-Yuan Cheng","doi":"10.1093/neuonc/noaf086","DOIUrl":"10.1093/neuonc/noaf086","url":null,"abstract":"<p><strong>Background: </strong>Isocitrate dehydrogenase mutant (IDH-mut) gliomas represent a distinct subtype of glioma, characterized by a relatively better prognosis compared to IDH wildtype (wt) glioblastoma (GBM). Despite this advantage, these tumors remain incurable due to the limited availability of effective treatments. Targeting SHP2, a non-receptor protein tyrosine phosphatase, is a promising therapeutic strategy for several types of human cancers. In this study, we aim to determine the efficacy of SHP inhibition in IDH-mut gliomas.</p><p><strong>Methods: </strong>Bioinformatic and biological analyses revealed increased expression and activation of the PDGFRA-SHP2-ERK pathway in clinical IDH-mut gliomas and patient-derived IDH-mut glioma stem-like cells (GSCs). The effects of SHP2 inhibition, alone or with radiation therapy (RT), were assessed through assays including cell growth, sphere formation, cell differentiation markers, flow cytometry, immunoblotting, immunohistochemistry, and orthotopic brain tumor xenografts.</p><p><strong>Results: </strong>PDGFRA expression was elevated in IDH-mut gliomas and GSCs, activating the SHP2-ERK pathway. SHP099, a SHP2 inhibitor, reduced GSC tumorigenicity in vitro and in vivo by disrupting SHP2-ERK signaling and promoting differentiation. SHP099 also enhanced cytotoxicity of RT, the standard treatment for IDH-mut glioma, in IDH-mut GSCs and orthotopic glioma models. Mechanistically, the PDGFRA-SHP2-ERK axis is activated in IDH-mut gliomas and RT further activates this pathway. Targeting SHP2 suppressed ERK signaling thereby enhancing the therapeutic effect of RT.</p><p><strong>Conclusion: </strong>Combining SHP2 inhibition with RT is a promising therapeutic avenue for IDH-mut glioma by suppressing the activated SHP2-ERK axis.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2023-2034"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701128","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":"Spatial transcriptomics: Advances and challenges in peripheral nerve sheath tumor.","authors":"Zirong Huo, Huipeng Li, Zhihua Zhang","doi":"10.1093/neuonc/noaf116","DOIUrl":"10.1093/neuonc/noaf116","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2088-2089"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030229","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":"An in-depth survey of immunosuppressive myeloid cell heterogeneity in gliomas.","authors":"Brandon Emanuel León, Defne Bayik","doi":"10.1093/neuonc/noaf080","DOIUrl":"10.1093/neuonc/noaf080","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1930-1931"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701055","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":"Emerging frontiers in diffuse intrinsic pontine glioma treatment: A new hope.","authors":"Eisha Anne Christian, James T Rutka","doi":"10.1093/neuonc/noaf117","DOIUrl":"10.1093/neuonc/noaf117","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2127-2128"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015277","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":"Salvage therapies for first relapse of SHH medulloblastoma in early childhood.","authors":"Craig Erker, Martin Mynarek, Marie Simbozel, Brandon T Craig, Virginia L Harrod, Andrea M Cappellano, Kenneth J Cohen, Vicente Santa-Maria Lopez, Andres Morales La Madrid, Chantel Cacciotti, Lorena Baroni, Ralph Salloum, Ashley S Margol, George Michaiel, Dolly Aguilera, Claire M Mazewski, Cassie N Kline, Jonathan L Finlay, Mohamed S Abdelbaki, Jeffrey C Murray, Kathleen Dorris, Bruce Crooks, Kevin F Ginn, Nisreen Amayiri, Stephan Tippelt, Gudrun Fleischhack, Svenja Tonn, Nicolas U Gerber, Alvaro Lassaletta, Jordan R Hansford, Sara Khan, Stephen W Gilheeney, Lindsey M Hoffman, Michal Zapotocky, Valérie Larouche, Shafqat Shah, Vijay Ramaswamy, Amar Gajjar, Sébastien Perreault, Sabine Mueller, Juliette Hukin, Sylvia Cheng, Zhihong J Wang, Kara Matheson, Simon Bailey, Eric Bouffet, Steven C Clifford, Giles Robinson, Christelle Dufour, Stefan Rutkowski, Lucie Lafay-Cousin","doi":"10.1093/neuonc/noaf092","DOIUrl":"10.1093/neuonc/noaf092","url":null,"abstract":"<p><strong>Background: </strong>Sonic hedgehog (SHH) medulloblastoma is the most common molecular group of infant and early childhood medulloblastoma (iMB) and has no standard of care at relapse. This work aimed to evaluate the post-relapse survival (PRS) and explore prognostic factors of patients with nodular desmoplastic (ND) and/or SHH iMB.</p><p><strong>Methods: </strong>This international retrospective study included 147 subjects diagnosed with relapsed ND/SHH iMB between 1995 and 2017, <6 years old at original diagnosis, and treated without initial craniospinal irradiation (CSI). Univariable and multivariable Cox models with propensity score analyses were used to assess PRS for those in the curative intent cohort.</p><p><strong>Results: </strong>The 3-year PRS was 61.6% (95% confidence interval [CI], 52.2-69.6). The median age at relapse was 3.4 years (interquartile range [IQR], 2.6-4.1). Those with local relapse (40.8%) more often received salvage treatment with surgery (P < .001), low-dose CSI (≤24 Gy; P < .001), or focal radiotherapy (P = .008). Patients not receiving CSI (40.5%) more often received salvage marrow-ablative chemotherapy (HDC + AuHCR [P < .001]). On multivariable analysis, CSI was associated with improved survival (hazard ratio [HR] 0.33 [95% CI, 0.13-0.86], P = .04). Salvage HDC + AuHCR, while clinically important, did not reach statistical significance (HR 0.24 [95% CI, 0.0054-1.025], P = .065).</p><p><strong>Conclusions: </strong>Survival of patients with relapsed SHH iMB is not satisfactory and relies on treatments associated with toxicities including CSI and/or HDC + AuHCR. Cure at initial diagnosis to avoid relapse is crucial. For patients with localized relapse undergoing resection, alternative salvage regimens that avoid high-dose CSI (>24 Gy) can be considered.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2158-2169"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788591","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":"High-precision radiotherapy achieves excellent long-term control and preserves function in pediatric craniopharyngioma-Subset analysis of a randomized trial.","authors":"Rakesh Jalali, Suman Ghosh, Abhishek Chatterjee, Savita Goswami, Nalini Shah, Debnarayan Dutta, Uday Krishna, Tejpal Gupta, Jayant S Goda","doi":"10.1093/neuonc/noaf049","DOIUrl":"10.1093/neuonc/noaf049","url":null,"abstract":"<p><strong>Background: </strong>The evolving treatment paradigm in children and adolescents with craniopharyngioma (CP) aims at minimizing late functional sequelae. Advanced radiotherapeutic techniques offer theoretical advantages of preserving neurological functions; however, clinical evidence of such is limited. The current study constitutes a secondary analysis of CP patients in a Randomized Control Trial testing Conventional RT (ConvRT) versus Stereotactic Conformal Radiotherapy (SCRT; NCT00517959).</p><p><strong>Methods: </strong>Eighty-two patients of CP (SCRT: 39, ConvRT: 43, Dose: 54 Gy in 30 fractions) were analyzed, assessing the clinical impact of dosimetric sparing on neurocognitive function, endocrine function, overall survival (OS) and local control (LC). Patients were longitudinally assessed from baseline through 5 years post-treatment using the Weschler Intelligence Score Chart/WAIS scales.</p><p><strong>Results: </strong>The median age was 13 years (IQR = 9-17 years). The 10-year OS and LC rates were 86.4% and 92.7%, respectively, with no significant difference between the arms. SCRT patients showed significant improvement in mean full-scale IQ (difference in slope = 3.3 points per year, P = .01) and performance quotient (difference in slope = 3.6, P = .04) compared to those treated with ConvRT. Freedom from cognitive decline (a 5-point drop) at 5 years was higher with SCRT (66.6% vs. 38.2%; HR = 0.41, P = .03). Younger age (<15 years) was a significant negative predictor of neurocognitive outcomes (P = .002). SCRT patients also experienced a lower cumulative incidence of new neuroendocrine dysfunction (25.7% vs. 48.8%, P = .029).</p><p><strong>Conclusions: </strong>SCRT offers excellent tumor control and similar survival with superior long-term preservation of neurocognitive and endocrine functions in CP patients compared to conventional RT. High-precision RT should constitute the standard of care in CP.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2147-2157"},"PeriodicalIF":13.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582350","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}