Neuro-oncology最新文献

{"title":"Locoregional Infusion of EGFR806-CAR T Cells for Recurrent or Refractory Pediatric CNS Tumors: Results of the Completed BrainChild02 Phase 1 Clinical Trial.","authors":"Juliane Gust, Bonnie L Cole, Rebecca Ronsley, Ashley L Wilson, Kristy Seidel, Jason Wendler, Sowmya Pattabhi, Christopher Brown, Stephanie D Rawlings-Rhea, Nadezhda Shtanukhina, Samuel R Browd, Jason S Hauptman, Amy Lee, Jeffrey G Ojemann, Erin E Crotty, Sarah E S Leary, Francisco A Perez, Jason N Wright, Catherine M Albert, Navin Pinto, Rebecca A Gardner, Nicholas A Vitanza, Michael C Jensen, Julie R Park","doi":"10.1093/neuonc/noaf064","DOIUrl":"https://doi.org/10.1093/neuonc/noaf064","url":null,"abstract":"<p><strong>Background: </strong>Relapsed/refractory pediatric CNS tumors have a poor prognosis. EGFR is commonly overexpressed, but EGFRvIII mutations are uncommon. To target these tumors, we used chimeric antigen receptor (CAR) T cells with a binder based on mAb806 which recognizes ectopically expressed wild-type EGFR and EGFRvIII.</p><p><strong>Methods: </strong>In this open-label phase 1 clinical trial, patients age 1-26 years with EGFR+ CNS tumors received weekly infusions of 1-2.5 x 107 CAR T cells into the tumor resection bed or the lateral ventricle via an implanted catheter. No lymphodepletion was used.</p><p><strong>Results: </strong>Eleven patients were enrolled. Four (3 with high-grade glioma, 1 with atypical teratoid-rhabdoid tumor) were treated and received 5-10 CAR T cell infusions without dose-limiting toxicities. The trial closed prior to reaching planned dose regimens. All treatment-related adverse events were no higher than CTCAE grade 2. The most common were headache and nausea. One patient had a grade 1 seizure, and three had new sensory changes, weakness and/or urinary changes (grade 1-2) that were possibly related to CAR T cell infusion. Three of the four treated patients had progressive disease. One patient with spinal cord diffuse midline glioma had progressive peritumoral edema that could not be conclusively attributed to either progression or pseudoprogression and was therefore defined as stable disease, followed by a complete response to subsequent chemotherapy.</p><p><strong>Conclusions: </strong>Intracranially infused EGFR806-CAR T cells were tolerable at tested doses, with a best response of stable disease. EGFR is a potentially useful target for cellular therapy against pediatric brain tumors, particularly high-grade gliomas.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605500","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":"Germline analysis of an international cohort of pediatric diffuse midline glioma patients.","authors":"Marion K Mateos, Pamela Ajuyah, Noemi Fuentes-Bolanos, Sam El-Kamand, Paulette Barahona, Ann-Kristin Altekoester, Chelsea Mayoh, Holly Holliday, Jie Liu, Louise Cui, Elke Pfaff, Alan Mackay, Adam C Resnick, Mark Pinese, Loretta M S Lau, Dong-Anh Khuong-Quang, Kimberly Dias, Catherine Goudie, Alison Salkeld, Jo Lynne Rokita, David T W Jones, Nikoleta Juretic, Elisha Hayden, Stefan M Pfister, Christof M Kramm, Mirjam Blattner-Johnson, Nada Jabado, Maria Tsoli, Orazio Vittorio, Sabine Mueller, Yiran Guo, Katherine Tucker, Sebastian M Waszak, Sebastien Perreault, Chris Jones, Marie Wong-Erasmus, Mark J Cowley, David S Ziegler","doi":"10.1093/neuonc/noaf061","DOIUrl":"https://doi.org/10.1093/neuonc/noaf061","url":null,"abstract":"<p><strong>Background: </strong>Factors that drive the development of diffuse midline gliomas (DMG) are unknown. Our study aimed to determine the prevalence of pathogenic/likely pathogenic (P/LP) germline variants in pediatric patients with DMG.</p><p><strong>Methods: </strong>We assembled an international cohort of 252 pediatric patients with DMG, including diffuse intrinsic pontine glioma (n=153), with germline whole genome or whole exome sequencing.</p><p><strong>Results: </strong>We identified P/LP germline variants in cancer predisposition genes in 7.5% (19/252) of patients. Tumor profiles differed, with absence of somatic drivers in the PI3K/mTOR pathway in patients with germline P/LP variants versus those without (P = 0.023). P/LP germline variants were recurrent in homologous recombination (n=9; BRCA1, BRCA2, PALB2) and Fanconi anemia genes (n=4). Somatic findings established that the germline variants definitively contributed to tumorigenesis in at least 1% of cases. One patient with recurrent DMG and pathogenic germline variants (BRCA2, FANCE) showed near-complete radiological response to PARP and immune checkpoint inhibition.</p><p><strong>Conclusions: </strong>Our study determined the prevalence of pathogenic germline variants in pediatric DMG, and suggests a role in tumorigenesis for a subset of patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605479","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":"Corrigendum to: Targeting the cell cycle to enhance chemotherapy efficacy in glioblastoma.","authors":"","doi":"10.1093/neuonc/noaf034","DOIUrl":"https://doi.org/10.1093/neuonc/noaf034","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597439","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":"Corrigendum to: Suppression of glioblastoma by targeting the overactivated protein neddylation pathway.","authors":"","doi":"10.1093/neuonc/noaf053","DOIUrl":"https://doi.org/10.1093/neuonc/noaf053","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597438","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":"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: 54Gy in 30 fractions) were analysed, 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 five years post-treatment using the WISC/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= 0.01) and performance quotient (difference in slope=3.6, p= 0.04) 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=0.03). Younger age (<15 years) was a significant negative predictor of neurocognitive outcomes (p=0.002). SCRT patients also experienced lower cumulative incidence of new neuroendocrine dysfunction (25.7% vs. 48.8%, p=0.029).</p><p><strong>Conclusion: </strong>SCRT offers excellent tumour 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":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamate dehydrogenase 1-catalytic glutaminolysis feedback activates EGFR/PI3K/AKT pathway and reprograms glioblastoma metabolism.","authors":"Rui Yang, Guanghui Zhang, Zhen Meng, Li Wang, Yanping Li, Haibin Li, Siyuan Yan, Xiaonan Wei, Shanshan Wang, Hongjuan Cui","doi":"10.1093/neuonc/noae222","DOIUrl":"10.1093/neuonc/noae222","url":null,"abstract":"<p><strong>Background: </strong>Glutamine is an important nutrient for cancer cell growth that provides biological sources for nucleic acid and fatty acid synthesis, but the role of glutaminolysis in signal transduction and glioblastoma (GBM) progression remains little known.</p><p><strong>Methods: </strong>Knockdown and overexpression cells were obtained to explore the functional roles of glutamate dehydrogenase 1 (GDH1) in cell proliferation, tumor formation, and aerobic glycolysis. RNA-seq, Chromatin immunoprecipitation, luciferase assay, and western blot were performed to verify the regulation of the EGFR-AKT pathway by the GDH1 (also known as GLUD1) and KDM6A. Metabolite-level measurements and Seahorse Assay were performed to assess the functional role of GHD1 in reprogramming glycolysis.</p><p><strong>Results: </strong>Here, we report that GDH1 catalytic glutaminolysis is essential for GBM cell line proliferation and brain tumorigenesis even in high-glucose conditions. Glutamine is metabolized through glutaminolysis to produce α-ketoglutarate (α-KG). We demonstrate that glutamine in combination with leucine activates mammalian TORC1 by enhancing glutaminolysis and α-KG production. α-KG increases the transcription of PDPK1 by reducing the suppressive histone modification H3K27me3 and then promotes the activation of the PI3K/AKT/mTOR pathway. This transcriptional activation induced by α-KG requires histone demethylase KDM6A, which is a 2-oxoglutarate oxygenase that plays an important role in converting α-KG to succinate. Furthermore, we show that GDH1-catalytic glutaminolysis also increases the expression of HK2 and promotes glycolysis in high-glucose conditions dependent on KDM6A-mediated demethylation of H3K27.</p><p><strong>Conclusions: </strong>These findings suggest a novel function of glutaminolysis in the regulation of signal transduction and metabolism reprogramming and provide further evidence for the unique role of glutaminolysis in GBM progression.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"668-681"},"PeriodicalIF":16.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504990","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":"EVA1-antibody drug conjugate is a new therapeutic strategy for eliminating glioblastoma-initiating cells.","authors":"Jiahui Hou, Tamami Uejima, Miho Tanaka, You Lee Son, Kazuharu Hanada, Mutsuko Kukimoto-Niino, Shigeru Yamaguchi, Shigeru Hashimoto, Shigeyuki Yokoyama, Toshitada Takemori, Takashi Saito, Mikako Shirouzu, Toru Kondo","doi":"10.1093/neuonc/noae226","DOIUrl":"10.1093/neuonc/noae226","url":null,"abstract":"<p><strong>Background: </strong>The discovery of glioblastoma (GBM)-initiating cells (GICs) has impacted GBM research. These cells are not only tumorigenic but also exhibit resistance to radiotherapy and chemotherapy. Therefore, it is crucial to characterize GICs thoroughly and identify new therapeutic targets. In a previous study, we successfully identified epithelial-V-like antigen 1 (EVA1) as a novel functional factor specific to GICs.</p><p><strong>Methods: </strong>Hybridoma cells were generated by immunizing BALB/c mice with EVA1-Fc fusion protein. The reactivity of the supernatant from these hybridoma cells was examined using EVA1-overexpressing cells and GICs. Candidate antibodies were further selected using Biacore surface plasmon resonance analysis and 2 cytotoxicity assays-antibody-dependent cell cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Among the antibodies, the cytotoxicity of the B2E5-antibody drug conjugate (B2E5-ADC) was evaluated by both adding it to cultured GICs and injecting it into GIC tumor-bearing brains.</p><p><strong>Results: </strong>B2E5 demonstrated a high affinity for human EVA1 and effectively killed both EVA1-expressing cell lines and GICs in culture through ADCC and CDC. B2E5-ADC also exhibited strong cytotoxicity to GICs in culture and prevented their tumorigenesis in the brain when administered intracranially to the tumor-bearing brain.</p><p><strong>Conclusion: </strong>Our data indicate that B2E5-ADC is a new and promising therapeutic strategy for GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"682-694"},"PeriodicalIF":16.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522459","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":"Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview.","authors":"Rupesh Kotecha, Alonso La Rosa, Paul D Brown, Michael A Vogelbaum, Pierina Navarria, Raphael Bodensohn, Maximilian Niyazi, Philipp Karschnia, Giuseppe Minniti","doi":"10.1093/neuonc/noae220","DOIUrl":"10.1093/neuonc/noae220","url":null,"abstract":"<p><p>As cancer patients with intracranial metastatic disease experience increasingly prolonged survival, the diagnosis and management of recurrent brain metastasis pose significant challenges in clinical practice. Prior to deciding upon a management strategy, it is necessary to ascertain whether patients have recurrent/progressive disease vs adverse radiation effect, classify the recurrence as local or distant in the brain, evaluate the extent of intracranial disease (size, number and location of lesions, and brain metastasis velocity), the status of extracranial disease, and enumerate the interval from the last intracranially directed intervention to disease recurrence. A spectrum of salvage local treatment options includes surgery (resection and laser interstitial thermal therapy [LITT]) with or without adjuvant radiotherapy in the forms of external beam radiotherapy, intraoperative radiotherapy, or brachytherapy. Nonoperative salvage local treatments also range from single fraction and fractionated stereotactic radiosurgery (SRS/FSRS) to whole brain radiation therapy (WBRT). Optimal integration of systemic therapies, preferably with central nervous system (CNS) activity, may also require reinterrogation of brain metastasis tissue to identify actionable molecular alterations specific to intracranial progressive disease. Ultimately, the selection of the appropriate management approach necessitates a sophisticated understanding of patient, tumor, and prior treatment-related factors and is often multimodal; hence, interdisciplinary evaluation for such patients is indispensable.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"597-615"},"PeriodicalIF":16.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569115","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":"Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: Lessons from the French POLA cohort.","authors":"Domique Figarella-Branger, Carole Colin, Karima Mokhtari, Emmanuelle Uro-Coste, Ahmed Idbaih, Romain Appay, Emeline Tabouret, Mehdi Touat, Antoine Seyve, Catherine Carpentier, Caroline Dehais, François Ducray","doi":"10.1093/neuonc/noae221","DOIUrl":"10.1093/neuonc/noae221","url":null,"abstract":"<p><strong>Background: </strong>In the POLA cohort, 3 pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis).</p><p><strong>Methods: </strong>494 patients from the POLA cohort, with a median follow-up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement (CE) in group 1 on overall survival (OS) or progression-free survival (PFS), survival curves were obtained (Kaplan-Meier method) and compared (log-rank test). The prognostic value of clinical factors and CDKN2A homozygous deletion HD were also tested. Multivariate analysis was performed.</p><p><strong>Results: </strong>Survival analysis demonstrated that the pathological groups were associated with both progression-free survival (PFS P = .01) and overall survival (OS P = .001). In group 1, patients with CE (1CE+) had a poorer prognosis compared to those without (OS P = .028, PFS P = .006). Further stratification into group 1CE-, group 1CE+, group 2, and group 3 provided clearer prognostic distinctions (OS P = .002, PFS P < .0001). Other prognostic factors included age (OS P < .0001, PFS P = .002), extent of surgical resection (OS P = .001, PFS P = .003), KPS (OS P < .0001, PFS P = 0.002), postoperative treatment (OS P = .007, PFS P < .0001), and CDKN2A HD (OS and PFS P < .0001). The pathological groups remained of prognostic significance for PFS in multivariate analysis.</p><p><strong>Conclusions: </strong>Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH-mutant, and 1p/19q co-deleted. Besides, in group 1 patients, lack of CE is a factor of better prognosis.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"755-766"},"PeriodicalIF":16.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471118","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":"ROR1 facilitates glioblastoma growth via stabilizing GRB2 to promote c-Fos expression in glioma stem cells.","authors":"Hongtao Zhu, Lidong Cheng, Dan Liu, Xiaoyu Ma, Zhiye Chen, Heng Fan, Ran Li, Yang Zhang, Hailong Mi, Jun Li, Suojun Zhang, Xingjiang Yu, Kai Shu","doi":"10.1093/neuonc/noae224","DOIUrl":"10.1093/neuonc/noae224","url":null,"abstract":"<p><strong>Background: </strong>Glioma stem cells (GSCs) are the root cause of tumorigenesis, recurrence, and therapeutic resistance in glioblastoma (GBM), the most prevalent and lethal type of primary adult brain malignancy. The exploitation of novel methods targeting GSCs is crucial for the treatment of GBM. In this study, we investigate the function of the novel ROR1-GRB2-c-Fos axis in GSCs maintenance and GBM progression.</p><p><strong>Methods: </strong>The expression characteristics of ROR1 in GBM and GSCs were assessed by bioinformatic analysis, patient specimens, and patient-derived GSCs. Lentivirus-mediated gene knockdown and overexpression were conducted to evaluate the effect of ROR1 on GSCs proliferation and self-renewal both in vitro and in vivo. The downstream signaling of ROR1 in GSCs maintenance was unbiasedly determined by RNA-seq and validated both in vitro and in vivo. Finally, rescue assays were performed to further validate the function of the ROR1-GRB2-c-Fos axis in GSCs maintenance and GBM progression.</p><p><strong>Results: </strong>ROR1 is upregulated in GBM and preferentially expressed in GSCs. Disruption of ROR1 markedly impairs GSC proliferation and self-renewal, and inhibits GBM growth in vivo. Moreover, ROR1 stabilizes GRB2 by directly binding and reducing its lysosomal degradation, and ROR1 knockdown significantly inhibits GRB2/ERK/c-Fos signaling in GSCs. Importantly, ectopic expression of c-Fos counteracts the effects caused by ROR1 silencing both in vitro and in vivo.</p><p><strong>Conclusions: </strong>ROR1 plays essential roles in GSCs maintenance through binding to GRB2 and activation of ERK/c-Fos signaling, which highlights the therapeutic potential of targeting the ROR1-GRB2-c-Fos axis.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"695-710"},"PeriodicalIF":16.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504992","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}