Neuro-oncology最新文献

{"title":"Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.","authors":"Geno Guerra, George Wendt, Lucie McCoy, Helen M Hansen, Linda Kachuri, Annette M Molinaro, Terri Rice, Victoria Guan, Lianne Capistrano, Allison Hsieh, Veruna Kalsi, Jaimie Sallee, Jennie W Taylor, Jennifer L Clarke, Eduardo Rodriguez Almaraz, John K Wiencke, Jeanette E Eckel-Passow, Robert B Jenkins, Margaret Wrensch, Stephen S Francis","doi":"10.1093/neuonc/noae275","DOIUrl":"10.1093/neuonc/noae275","url":null,"abstract":"<p><strong>Background: </strong>Temozolomide (TMZ) treatment has demonstrated a variable impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.</p><p><strong>Methods: </strong>We evaluated TMZ-related survival associations of pathogenic germline SNPs and genetically predicted transcript levels within 34 DNA repair genes among 1504 glioma patients from the University of California San Francisco Adult Glioma Study (UCSF AGS) and Mayo Clinic, whose diagnoses spanned pre- and post-TMZ eras within the major known glioma prognostic molecular subtypes.</p><p><strong>Results: </strong>Among those who received TMZ, 5 SNPs were associated with overall survival, but not in those who did not receive TMZ. Only rs2308321-G, in MGMT, was associated with decreased survival (hazard ratio = 1.21, P = .019) for all glioma subtypes. Rs73191162-T (near UNG), rs13076508-C (near PARP3), rs7840433-A (near NEIL2), and rs3130618-A (near MSH5) were only associated with survival and TMZ treatment for certain subtypes, suggesting subtype-specific germline chemosensitization. Genetically predicted elevated expression of PNKP, compared to normal brain expression, was associated with markedly poor survival in TMZ-treated patients with isocitrate dehydrogenase (IDH)-mutant and 1p/19q non-codeleted gliomas (P = .015), with a median difference of over 70 months in overall survival times. Similarly, NEIL2 and TDG expressions were associated with altered TMZ-related survival only among certain subtypes.</p><p><strong>Conclusions: </strong>Functional germline alterations within DNA repair genes were associated with TMZ sensitivity, measured by overall survival among adults with glioma. These variants should be evaluated in prospective analyses and functional studies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1385-1398"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922260","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":"A hitchhiker's guide to cerebrospinal fluid biomarkers for neuro-oncology.","authors":"Cecile Riviere-Cazaux, Michael B Keough, Jeffrey A Zuccato, Rahul Kumar, Sebastian Schulz, Arthur E Warrington, Michael W Ruff, Benjamin M Ellingson, Nader Sanai, Jian L Campian, Sani H Kizilbash, Ian F Parney, Gelareh Zadeh, Mustafa Khasraw, Tobias Kessler, Ugur Sener, Daniel P Cahill, Alireza Mansouri, Terry C Burns","doi":"10.1093/neuonc/noae276","DOIUrl":"10.1093/neuonc/noae276","url":null,"abstract":"<p><p>Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection. Moreover, radiographic features, such as tumor-CSF contact and blood-brain barrier disruption, are critical covariates that may affect biomarker detection and the abundance of plasma-derived analytes in CSF, respectively. Longitudinal intracranial CSF sampling, enabled by access devices like Ommaya reservoirs, may offer a window into treatment response and disease progression, though variability in analyte yield, sample volumes, and the dynamic effects of surgical resection pose challenges. This review critically evaluates the anatomic, radiographic, and longitudinal factors, or \"time-space continuum,\" that impact glioma CSF biomarker abundance. Practical considerations for longitudinal CSF biobanking, including access device placement and collection, are also reviewed. Key takeaways and recommendations for CSF glioma biomarker discovery and validation are provided as a \"hitchhiker's guide\" based on our collective experience, along with resources for investigators aiming to develop CSF biobanking at their institutions.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1165-1179"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952455","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":"Disease stage-specific role of the mitochondrial pyruvate carrier suppresses differentiation in temozolomide and radiation-treated glioblastoma.","authors":"Emma Martell, Helgi Kuzmychova, Harshal Senthil, Ujala Chawla, Esha Kaul, Akaljot Grewal, Versha Banerji, Christopher M Anderson, Chitra Venugopal, Donald Miller, Tamra E Werbowetski-Ogilvie, Sheila K Singh, Tanveer Sharif","doi":"10.1093/neuonc/noaf008","DOIUrl":"10.1093/neuonc/noaf008","url":null,"abstract":"<p><strong>Background: </strong>The mitochondrial pyruvate carrier (MPC), a central metabolic conduit linking glycolysis and mitochondrial metabolism, is instrumental in energy production. However, the role of the MPC in cancer is controversial. In particular, the importance of the MPC in glioblastoma (GBM) disease progression following standard temozolomide (TMZ) and radiation therapy (RT) remains unexplored.</p><p><strong>Methods: </strong>Leveraging in vitro and in vivo patient-derived models of TMZ-RT treatment in GBM, we characterize the temporal dynamics of MPC abundance and downstream metabolic consequences using state-of-the-art molecular, metabolic, and functional assays.</p><p><strong>Results: </strong>Our findings unveil a disease stage-specific role for the MPC, where in posttreatment GBM, but not therapy-naïve tumors, the MPC acts as a central metabolic regulator that suppresses differentiation. Temporal profiling reveals a dynamic metabolic rewiring where a steady increase in MPC abundance favors a shift towards enhanced mitochondrial metabolic activity across patient GBM samples. Intriguingly, while overall mitochondrial metabolism is increased, acetyl-CoA production is reduced in posttreatment GBM cells, hindering histone acetylation and silencing neural differentiation genes in an MPC-dependent manner. Finally, the therapeutic translations of these findings are highlighted by the successful pre-clinical patient-derived orthotopic xenograft trials utilizing a blood-brain-barrier permeable MPC inhibitor, MSDC-0160, which augments standard TMZ-RT therapy to mitigate disease relapse and prolong animal survival.</p><p><strong>Conclusion: </strong>Our findings demonstrate the critical role of the MPC in mediating GBM aggressiveness and molecular evolution following standard TMZ-RT treatment, illuminating a therapeutically-relevant metabolic vulnerability to potentially improve survival outcomes for GBM patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1193-1209"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971767","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":"Establishing a living biobank of pediatric high-grade glioma and ependymoma suitable for cancer pharmacology.","authors":"Clémence Deligne, Arthur Tourbez, Flavie Bénard, Swann Meyer, Alexis Curt, Matteo Gianesello, Maud Hamadou, Léna Clavier, Claire Coquet, Charlotte Bocquet, Julia Tomine, Thomas Diot, Hermes Paraqindes, Virginie Marcel, Clément Berthelot, Justine Engel, Isabelle Rochet, Marc Barritault, Clara Savary, Nicolas Gadot, Valéry Attignon, Marjorie Carrere, Marc Billaud, Aurélie Dutour, Martine Cordier-Bussat, Pierre-Aurélien Beuriat, Alexandru Szathmari, Federico Di Rocco, Jean-Yves Blay, Luca Tiberi, Alexandre Vasiljevic, David Meyronet, Marie Castets, Pierre Leblond, Laura Broutier","doi":"10.1093/neuonc/noaf007","DOIUrl":"10.1093/neuonc/noaf007","url":null,"abstract":"<p><strong>Background: </strong>Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help define new therapeutic options for pediatric brain tumors.</p><p><strong>Methods: </strong>Through an integrative approach based on our expertise and a careful review of the literature about glioblastoma 3D primary cultures, we set up a standardized methodological pipeline for the establishment, characterization, and biobanking of PDT-O through direct 3D in vitro culture of the deadliest pediatric glial brain tumors. To assess PDT-O fidelity and validate their preclinical relevance, we performed comprehensive histological, molecular, and drug-response analyses.</p><p><strong>Results: </strong>Our methodological pipeline allowed the rapid and efficient generation of PDT-O recapitulating their parental tumor features, including intratumoral heterogeneity, even after several passages and cryopreservation/revival as 3D cultures. Moreover, we successfully performed preclinical test responses on these PDT-O to standard-of-care therapies and new therapeutic options. Finally, we identified ONC201 as a selective drug for pediatric glial tumor types not restricted to H3K27-altered glial tumors, as well as combination strategies to increase the therapeutic response to ONC201.</p><p><strong>Conclusions: </strong>Hence, we describe a fast and robust process to biobank PDT-O for pediatric glial brain tumors. These PDT-O models have the potential for patient-specific modeling even after long-term expansion in vitro, and we established the proof-of-concept of their usefulness to support powerful preclinical studies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1325-1340"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952457","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":"Lineage dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and -independent immunotherapeutic targets.","authors":"Nathan M Kendsersky, Michal Odrobina, Nathaniel W Mabe, Alvin Farrel, Liron Grossmann, Matthew Tsang, David Groff, Adam J Wolpaw, Alaa Narch, Francesca Zammarchi, Patrick H van Berkel, Chi V Dang, Yaël P Mossé, Kimberly Stegmaier, John M Maris","doi":"10.1093/neuonc/noaf012","DOIUrl":"10.1093/neuonc/noaf012","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)-like cells and therapy-resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state-specific targetable cell surface proteins.</p><p><strong>Methods: </strong>We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets. Targets were validated with ChIP-sequencing, immunoblotting, and flow cytometry in neuroblastoma cell lines and isogenic ADRN-to-MES transition cell line models. Finally, we evaluated the activity of MES-specific agents in vivo and in vitro.</p><p><strong>Results: </strong>Most immunotherapeutic targets being developed for neuroblastoma showed significantly higher expression in the ADRN subtype with limited expression in MES-like tumor cells. In contrast, CD276 (B7-H3) and L1CAM maintained expression across both ADRN and MES states. We identified several receptor tyrosine kinases (RTKs) enriched in MES-dominant samples and showed that AXL targeting with ADCT-601 was potently cytotoxic in MES-dominant cell lines and showed specific antitumor activity in a MES cell line-derived xenograft.</p><p><strong>Conclusions: </strong>Immunotherapeutic strategies for neuroblastoma must address the potential of epigenetic downregulation of antigen density as a mechanism for immune evasion. We identified several RTKs as candidate MES-specific immunotherapeutic target proteins for the elimination of therapy-resistant cells. We hypothesize that the phenomena of immune escape will be less likely when targeting pan-neuroblastoma cell surface proteins such as B7-H3 and L1CAM, and/or dual targeting strategies that consider both the ADRN and MES cell states.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1372-1384"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008972","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":"Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small-cell lung cancer better preserves white matter networks compared to conventional PCI.","authors":"Rob Colaes, Jeroen Blommaert, Maarten Lambrecht, Michiel B de Ruiter, Pim Pullens, Dirk de Ruysscher, José Belderbos, Stefan Sunaert, Sanne B Schagen, Sabine Deprez","doi":"10.1093/neuonc/noae271","DOIUrl":"10.1093/neuonc/noae271","url":null,"abstract":"<p><strong>Background: </strong>Hippocampal avoidance during prophylactic cranial irradiation (HA-PCI) is proposed to reduce neurocognitive decline, while preserving the benefits of PCI. We evaluated whether (HA-)PCI induces changes in white matter (WM) microstructure and whether sparing the hippocampus has an impact on preserving brain network topology. In addition, we evaluated associations between topological metrics with hippocampal volume and neuropsychological outcomes.</p><p><strong>Methods: </strong>In this multicenter randomized phase 3 trial (NCT01780675), small-cell lung cancer (SCLC) patients underwent neuropsychological testing and diffusion tensor imaging (DTI) before, 4 months (33 PCI, 37 HA-PCI) and 1 year (19 PCI, 17 HA-PCI) after (HA-)PCI. Changes in WM microstructure were investigated using whole-brain voxel-based analysis of fractional anisotropy (FA) and mean diffusivity (MD). Both hippocampal and whole-brain graph measures were used to evaluate the topological organization of structural networks. Correlation analysis was performed to associate topological metrics with neuropsychological outcomes and hippocampal volume.</p><p><strong>Results: </strong>Both HA-PCI and PCI were associated with decreased FA in major WM tracts, such as the corpus callosum, at 4 months and 1 year post-treatment. While these FA decreases did not differ significantly between treatment groups, only PCI demonstrated increased MD over time. In addition, PCI showed decreased global efficiency and increased characteristic path length over time when compared with HA-PCI. Significant correlations were found between whole-brain graph measures and neuropsychological outcomes.</p><p><strong>Conclusion: </strong>While both techniques induce important changes in the WM microstructure, HA-PCI might better preserve the topological organization of brain networks than PCI. The neuroprotective role of hippocampal sparing still needs further investigation.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1285-1296"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886102","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":"Plasmablast-like lymphoma cells as a distinct subpopulation confers multidrug resistance in PCNSL.","authors":"Feng Liang, Xiaotao Zhang, An Ping, Yichen Gu, Ziyang Jin, Huaming Li, Lingxiao Lu, Fan Yang, Junjie Wang, Jianan Lu, Feng Zhou, Jinfang Xu, Jingsen Chen, Junming Zhu, Fengqiang Liu, Jianmin Zhang, Ligen Shi","doi":"10.1093/neuonc/noaf154","DOIUrl":"https://doi.org/10.1093/neuonc/noaf154","url":null,"abstract":"<p><strong>Background: </strong>Primary central nervous system lymphoma (PCNSL) is a highly aggressive subtype of non-Hodgkin lymphoma that is confined to the central nervous system. PCNSL is associated with a poor 5-year survival rate of 30-40%, partly due to a high recurrence rate of 60%. A comprehensive understanding of the molecular signatures and mechanisms underlying drug resistance in PCNSL is crucial, as it has significant implications for therapeutic strategies.</p><p><strong>Methods: </strong>A cohort of 56 newly diagnosed PCNSL patients was generated. The tumor specimens were obtained by biopsy. A combined approach, including single-cell transcriptomics and B-cell receptor sequencing, transcriptome-informed multiplex immunohistochemistry, and ex-vivo drug response assays, was applied to reveal the transcriptional and immune microenvironment landscape of PCNSL.</p><p><strong>Results: </strong>We identify four main B cell subtypes, each characterized by distinct transcriptomic profiles, from malignant B cells in PCNSL. Among these subtypes, plasmablast-like lymphoma cells (PBLCs), characterized by upregulated genes typically associated with plasma cell differentiation, comprise 1.3%-8.1% of malignant B cells and correlate with poor prognosis in PCNSL. PBLCs exhibit reduced expression of CD20, Bruton tyrosine kinase, and FAS, resulting in drug resistance and immune evasion. In addition, PBLCs elevate the expression of critical transcription factors, including XBP1 and PRDM1, to maintain their phenotype. Clinical drugs, such as Lenalidomide, demonstrate potential cytotoxic effects on PBLCs.</p><p><strong>Conclusions: </strong>These findings highlight PBLCs as a distinct subtype of malignant B cells that plays a critical role in the multidrug resistance of PCNSL and reveal the molecular signature of PBLCs that can be targeted for therapy.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.","authors":"Macarena I de la Fuente, Mehdi Touat, Martin J van den Bent, Matthias Preusser, Katherine B Peters, Robert J Young, Raymond Y Huang, Benjamin M Ellingson, David Capper, Joanna J Phillips, Lia M Halasz, Helen A Shih, Roberta Rudà, Mary Jane Lim-Fat, Deborah T Blumenthal, Michael Weller, Yoshiki Arakawa, James R Whittle, François Ducray, David A Reardon, Wenya Linda Bi, Giuseppe Minniti, Rifaquat Rahman, Shawn Hervey-Jumper, Susan M Chang, Patrick Y Wen","doi":"10.1093/neuonc/noae259","DOIUrl":"10.1093/neuonc/noae259","url":null,"abstract":"<p><p>Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence. Consequently, there is an urgent need for innovative strategies that delay progression and the use of radiation therapy and chemotherapy. The recent Federal Drug Administration (FDA) approval of vorasidenib, a brain-penetrant small molecule targeting mutant IDH1/2 proteins, heralds a shift in the therapeutic landscape for IDH-mutant gliomas. In this review, we address the role of vorasidenib in the treatment of IDH-mutant gliomas, providing a roadmap for its incorporation into daily practice. We discuss ongoing clinical trials with vorasidenib and other IDH inhibitors, as single-agent or in combination with other therapies, as well as current challenges and future directions.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1135-1148"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896310","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":"From bench to bedside: Novel TGFβR1 inhibitor shows promise in neurofibromatosis treatment.","authors":"Jian Wang, Rolf Bjerkvig","doi":"10.1093/neuonc/noaf054","DOIUrl":"10.1093/neuonc/noaf054","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1256-1257"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020752","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":"Nanoparticle encapsulation enables systemic IGF-Trap delivery to inhibit intracerebral glioma growth.","authors":"Yinhsuan Michely Chen, Julien Chambon, Alexandre Moquin, Masakazu Hashimoto, Stephanie Perrino, Matthew Leibovitch, Yasmine Benslimane, Orçun Haçariz, Qin Yang, Ichiro Nakano, Brian Meehan, Janusz Rak, Stéphane Gagné, Pnina Brodt","doi":"10.1093/neuonc/noaf011","DOIUrl":"10.1093/neuonc/noaf011","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma. We previously reported that the intracerebral growth of glioma cells with reduced IGF-1R levels was inhibited. The objectives of this study were to evaluate the sensitivity of glioma cells to a novel IGF-axis inhibitor, the IGF-Trap, and optimize its delivery to the brain.</p><p><strong>Methods: </strong>We tested the effect of the IGF-Trap on the growth of the human glioma stem cells MES-1123 and U87 MG cells, and of murine GL261 cells in vivo, using subcutaneous and orthotopic implantation.</p><p><strong>Results: </strong>We show that the growth of glioma cells implanted subcutaneously or orthotopically in the brain was inhibited by systemic and direct intracerebral administration of IGF-Trap, respectively, resulting in increased survival. To increase the efficiency of systemic delivery to the brain, we encapsulated the IGF-Trap in trimethyl chitosan (TRIOZAN™) nanoparticles prior to intravenous injection. We found that nanoparticle encapsulation increased the uptake and retention of the IGF-Trap in the brain and resulted in an improved therapeutic effect against intra-cerebrally growing tumors.</p><p><strong>Conclusion: </strong>Our results identify the IGF-Trap as a potent inhibitor of intracerebral glioma growth and show that encapsulation in nanoparticles can improve delivery of biologics such as the IGF-Trap to the brain, thereby enhancing the therapeutic response.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1227-1240"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067038","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}