bims-malgli Biomed News
on Biology of malignant gliomas
Issue of 2026–07–19
eight papers selected by
Oltea Sampetrean, Keio University
  1. Differences in Primary Molecular Subtype Distribution Contribute to Racial and Ethnic Disparities in Adult-Type Diffuse Gliomas.
  2. Brain Network Connectivity Predicts Survival in Diffuse Midline Glioma.
  3. Integrating androgen signaling tumor dependency with host neuroendocrine immunity for glioblastoma therapies.
  4. ROS produced in mitochondria entrapped by self-assembly peptide fibers for target therapy of glioma.
  5. Uncovering MYOF as a novel therapeutic target in glioblastoma: mechanistic insights and drug discovery.
  6. Anti-CAR Immunity Drives Acquired Therapeutic Resistance to GD2-CAR T Cell Therapy in Diffuse Midline Glioma.
  7. Glioblastoma subtypes exhibit distinct migration mechanics and immune responses.
  8. FUS-mediated BBB opening reshapes plasma extracellular vesicle size distribution without elevating concentration in glioblastoma patients.
  1. Neuro Oncol. 2026 Jul 14. pii: noag157. [Epub ahead of print]
    Differences in Primary Molecular Subtype Distribution Contribute to Racial and Ethnic Disparities in Adult-Type Diffuse Gliomas.
    David Gomez, Ishan Shah, David J Cote, Mackenzie Price, Julia R Benedetti, John Pham, Carol Kruchko, Robert G Briggs, Gabriel Zada, Quinn T Ostrom.
       BACKGROUND: Molecular profiling has become an integral part of glioma classification. The extent to which incidence of molecularly-defined adult-type gliomas vary by demographics is unknown. We describe national-level incidence and overall survival patterns of selected glioma subtypes by race/ethnicity.
    METHODS: We generated standardized average annual age-adjusted incidence rates of molecularly-defined glioma subtypes by race/ethnicity from the Central Brain Tumor Registry of the United States (CBTRUS) using newly-diagnosed cases from January 1, 2018 to December 31, 2022. Survival data from the National Cancer Database (NCDB) were used from newly-diagnosed cases from January 1, 2018 to December 31, 2021 (with follow up through December 31, 2022) to evaluate four-year overall survival, median survival, and multivariable Cox Proportional hazards ratios.
    RESULTS: CBTRUS identified 68,172 glioma cases, IDH-wildtype glioblastoma was most common (n = 51,548). Non-Hispanic White individuals had significantly higher incidence of all gliomas compared to other groups (p > 0.001). Non-Hispanic Black individuals had the lowest incidence for IDH-mutant astrocytoma and oligodendroglioma, and shared lowest incidence of IDH-mutant glioblastoma and IDH-wildtype astrocytoma with non-Hispanic other individuals, who had the lowest incidence of IDH-wildtype glioblastoma (p < 0.001). The odds of having an IDH-wildtype (versus IDH-mutant) astrocytoma or glioblastoma were significantly lower for males, those of older age, and non-Hispanic Black individuals (p < 0.001). Non-Hispanic other individuals also had increased adjusted overall survival for most glioma subtypes compared to other racial/ethnic groups (p < 0.001). Four-year overall survival was lowest in all racial/ethnic groups for IDH-wildtype glioblastoma (p < 0.001).
    CONCLUSIONS: Our findings reveal significant disparities in incidence and survival by race/ethnicity with notable variations present based on glioma biomarkers.
    Keywords:  biomarkers; central brain tumor registry; disparity; glioma
    DOI:  https://doi.org/10.1093/neuonc/noag157
  2. Cancer Discov. 2026 Jul 16. OF1
    Brain Network Connectivity Predicts Survival in Diffuse Midline Glioma.
      
    DOI:  https://doi.org/10.1158/2159-8290.CD-RW2026-066
  3. Neuro Oncol. 2026 Jul 11. pii: noag156. [Epub ahead of print]
    Integrating androgen signaling tumor dependency with host neuroendocrine immunity for glioblastoma therapies.
    Iris Lavon, Alexander Lossos, Nima Sharifi, Justin D Lathia.
      
    DOI:  https://doi.org/10.1093/neuonc/noag156
  4. Proc Natl Acad Sci U S A. 2026 Jul 21. 123(29): e2518967123
    ROS produced in mitochondria entrapped by self-assembly peptide fibers for target therapy of glioma.
    Suling Zhang, Fanchen Yu, Yang Yang, Yi Jia, Yongqiang Xu, Jin Zhou, Zeng-Ying Qiao, Jin Lu, Chunmei Li, Hao Wang, Junbai Li.
      Brain glioma is a highly energy-dependent malignant tumor. Sonodynamic therapy (SDT) provides a noninvasive and effective approach for brain glioma therapy. Reactive oxygen species (ROS) from sonosensitizers in the treatment of SDT play a key role. Inspired by spider webs, a self-assembling "spider peptide" (P1) bearing porphyrin moieties was constructed to generate ROS under ultrasound. In glioma cells, P1 forms web-like nanofibers that weave around mitochondria and enables ROS to release in situ. This efficiently disrupts the energy metabolism of mitochondria leading to the inhibition of glioma cells growth. Glioma-derived exosomes loaded with peptide P1 (Evs@P1) exhibit enhanced blood-brain barrier permeability and homotypic targeting to glioma cells. After endocytic uptake, Evs@P1 complexes undergo hydrolysis in the acidic lysosomal environment exposing the mitochondrial-targeting peptide. Ultrasound enhances the rate of peptide self-assembly into nanofibers, which are extruded from the exosomes and weave around the mitochondrial surface. Such an assembly of P1 nanofibers accelerates the ROS generation, which is 3.7 times higher than that in the monomeric state. It indicates an effective method to prevent glioma growth in mice brains in vivo.
    Keywords:  ROS; molecular biomimetic; peptide; supramolecular assembly; target therapy
    DOI:  https://doi.org/10.1073/pnas.2518967123
  5. Cell Death Discov. 2026 Jul 14.
    Uncovering MYOF as a novel therapeutic target in glioblastoma: mechanistic insights and drug discovery.
    Peiqi Zhao, Zhen Chen, Jiajie Zhu, Zibin Zhang, Zhenqiu Xing, Fan Tang, Kankai Wang, Ying Zhang, Hong Chen, Qichuan Zhuge, Jianjing Yang.
      Glioblastoma (GBM) is the most common type of primary malignant brain tumor, characterized by a poor prognosis, high recurrence rate, and elevated mortality. In recent years, gene-targeted therapies leveraging small molecule compounds have gained momentum as a promising avenue for GBM intervention. Myoferlin (MYOF), a type II membrane protein of the Ferlin family, has emerged as a key regulator of membrane dynamics-governing processes such as vesicular trafficking, endocytosis, and membrane repair. In this study, we explore the previously uncharted role of MYOF in GBM progression and its potential as a diagnostic and therapeutic target. Our data reveal that silencing MYOF markedly suppresses glioma growth both in vitro and in vivo. Mechanistically, MYOF knockdown disrupts the nuclear translocation of phosphorylated STAT3 (P-STAT3), a critical oncogenic signaling event. Notably, we identified Entacapone (ENT), a small molecule capable of targeting MYOF, which significantly impedes glioma development across experimental models. These findings position MYOF as a novel molecular lever in GBM pathogenesis and highlight ENT as a potential therapeutic agent that exerts anti-glioma effects by blocking MYOF-mediated P-STAT3 nuclear import.The diagram illustrates a novel regulatory mechanism of IL-6/STAT3 signaling involving MYOF. Upon IL-6 stimulation, STAT3 undergoes phosphorylation. MYOF then binds to phosphorylated STAT3 and facilitates its translocation into the nucleus to regulate target gene expression. The compound ENT acts as a targeted inhibitor of this process by binding to MYOF, thereby blocking the nuclear transport of phosphorylated STAT3 and suppressing downstream signaling.
    DOI:  https://doi.org/10.1038/s41420-026-03254-0
  6. medRxiv. 2026 Jul 09. pii: 2026.06.25.26356492. [Epub ahead of print]
    Anti-CAR Immunity Drives Acquired Therapeutic Resistance to GD2-CAR T Cell Therapy in Diffuse Midline Glioma.
    Yiyun Chen, Kevin Reynolds, Maximilian R A Koch, Camille F Petrakian, Zinaida Good, Sean Yamada-Hunter, Elena Sotillo, Kun-Wei Song, Jasia Mahdi, Robbie Majzner, Moksha H Desai, Ying-Wen Huang, Hossein Daghagh, Zachary J Ehlinger, Nadya Iswari, Chiara Sabatti, Christina Baggott, Skyler P Rietberg, Kelvin C Mo, Kristin C Y Tsui, Mark P Hamilton, Emily Egeler, Jennifer Moon, Courtney Erickson, Ashley Jacobs, Allison K Duh, Barbara Beebe, Casey Carr, Michelle Fujimoto, Michael Kunicki, Alexandria S Lim, Amy Li, Annie K Brown, Adam Kuo, Aanchal Kaur, Smriti R Soundaranayagi, Snehit Prabhu, Gerald Grant, Laura M Prolo, Cynthia Campen, Sonia Partap, Kara L Davis, Steven A Feldman, Ramya Tunuguntla, Jennifer R Cochran, Bita Sahaf, Sabine Heitzeneder, Michelle Monje, Sneha Ramakrishna, Crystal Mackall.
      GD2-CAR T cell therapy has demonstrated clinical benefit in patients with H3K27M + diffuse midline glioma (DMG), but the durability of response has been limited in many patients 1,2 . To identify mechanisms of therapeutic resistance, we conducted longitudinal single-cell RNA and TCR sequencing of cerebrospinal fluid (CSF) lymphocytes from DMG patients receiving intravenous followed by sequential intracerebral GD2-CAR therapy, with lymphodepleting chemotherapy administered once prior to the start of CAR T cell therapy ( NCT04196413 ). CSF GD2-CAR T cells manifested limited persistence and clonal expansion, while non-engineered CSF lymphocytes underwent significant clonal expansion and repertoire stabilization, ultimately dominating the CSF immune compartment. Concurrently, peripheral blood CD4 + and CD8 + T cells manifested anti-CAR immune reactivity targeting epitopes enriched within murine-derived and engineered junctional regions of the CAR construct. This was associated with appearance of circulating Human Anti-CAR Antibodies (HACAs) that bound cells expressing the GD2-CAR, as well as clonal expansion of CSF B cells which produced HACA which impeded the cytotoxic activity of GD2-CAR T cells. In several cases, appearance of circulating HACA temporally correlated with disease progression and across the patient population, and levels of circulating HACA inversely correlated with circulating CAR T cell persistence. These findings reveal robust induction of systemic and CNS adaptive T cell and B cell responses to GD2-CAR T cells following intravenous then sequential intracerebroventricular GD2-CAR therapy and provide strong evidence that anti-CAR immunity is a significant contributor to therapeutic resistance in this setting.
    DOI:  https://doi.org/10.64898/2026.06.25.26356492
  7. Cancer Res Commun. 2026 Jul 14.
    Glioblastoma subtypes exhibit distinct migration mechanics and immune responses.
    Ghaidan A Shamsan, Chao J Liu, Brooke C Braman, Ruyi Li, Susan K Rathe, Aaron L Sarver, Nima Ghaderi, Mariah McMahon, Rebecca L Klank, Barbara R Tschida, S Joseph McFarren, Pamela C Rosato, David Masopust, Jann N Sarkaria, H Brent Clark, Steven Rosenfeld, David A Largaespada, David J Odde.
      Glioblastoma remains a deadly cancer driven in part by invasion of tumor cells into the brain. Transcriptomic analyses have identified distinct molecular subtypes, but mechanistic differences that account for clinical differences are not clear. Here, we show that, as predicted by the motor-clutch model of cell migration, mesenchymal glioma cells are more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. Despite their rapid migration and comparable proliferation rates in vitro, mice with mesenchymal tumors survive longer than those with proneural tumors. This improved survival correlated with an immune response in the mesenchymal tumors, including T cell-mediated. Consistently, inducing mesenchymal tumors in immunodeficient mice resulted in shorter survival supporting a protective immune role in mesenchymal tumors. Thus, mesenchymal tumors have aggressive migration, but are immunologically 'hot' which suppresses net proliferation. These two features counteract each other and may explain the lack of a strong survival difference between subtypes clinically, while also opening up new opportunities for subtype-specific therapies.
    DOI:  https://doi.org/10.1158/2767-9764.CRC-25-0579
  8. Neuro Oncol. 2026 Jul 14. pii: noag155. [Epub ahead of print]
    FUS-mediated BBB opening reshapes plasma extracellular vesicle size distribution without elevating concentration in glioblastoma patients.
    Massimiliano Del Bene, Daniela Osti, Marta Bonada, Riccardo Pascuzzo, Annica Piccardi, Giovanni Carone, Lisa Meanti, Mario Stanziano, Valentina Caldiera, Carla Carozzi, Antonio Silvani, Elisa Francesca Maria Ciceri, Marina Grisoli, Giuliana Pelicci, Francesco DiMeco.
       BACKGROUND: Focused ultrasound-mediated blood-brain barrier opening (BBBO) is hypothesized to enhance liquid biopsy by facilitating the release of tumor material into the circulation. This study aimed to evaluate the impact of MR-guided FUS-BBBO on plasma extracellular vesicle (EV) concentrations and size distributions, alongside cell-free DNA (cfDNA) profiles, to determine the clinical efficacy of this approach in glioblastoma (GB) patients.
    METHODS: We performed 14 MR-guided focused ultrasound (FUS)-BBBO procedures in patients with GB with blood sampling 1 h before and 1 h after sonication. Plasma EVs were isolated by size-exclusion chromatography and quantified by tunable resistive pulse sensing technology. Cell-free DNA (cfDNA) concentration and fragment profiles were assessed using fluorometric and electrophoretic methods.
    RESULTS: EV concentration showed no consistent change after FUS-BBBO, with marked inter-patient and inter-procedure heterogeneity. In contrast, EV size displayed a reproducible diameter reduction of ∼8-10 nm, driven predominantly by contraction of the upper tail of the size distribution, indicating selective modulation of larger vesicle subpopulations. cfDNA concentrations and fragmentation showed a heterogeneous pattern, with occasional patient-specific increases. Exploratory analyses revealed no significant associations between biomarker changes and procedural parameters except for treated volume.
    CONCLUSIONS: Our findings challenge the assumption that clinical BBBO uniformly increases biomarker abundance. The consistent shift toward smaller EVs suggests a selective modulation rather than an increased release. While BBBO may enhance the detectability of analytes that poorly cross the BBB, this may not apply to EVs, which are able to traverse the BBB under physiological conditions, further supporting their value as liquid-biopsy substrates in neuro-oncology. Future studies integrating clinical data with mechanistic models are necessary to refine FUS-enhanced diagnostic strategies.
    Keywords:  Blood-Brain Barrier Opening; Extracellular vesicles; Focused ultrasound; Glioblastoma; Liquid biopsy
    DOI:  https://doi.org/10.1093/neuonc/noag155
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