Glioblastoma (GBM) remains one of the most challenging brain tumors to treat, with a median overall survival of only 12-15 months. Recent studies have explored innovative immunotherapeutic strategies to address recurrent GBM (rGBM). A phase 1 trial by Bagley et al. investigated the intracerebroventricular delivery of bivalent CAR T cells targeting EGFR and IL-13Rα2, demonstrating promising safety and initial efficacy in patients with EGFR-amplified rGBM (ref: Bagley doi.org/10.1038/s41591-025-03745-0/). Similarly, Thompson et al. reported on a peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma, showing that this approach is both safe and immunogenic (ref: Thompson doi.org/10.1038/s43018-025-00998-z/). These findings highlight the potential of personalized immunotherapies in treating aggressive brain tumors. Moreover, the tumor microenvironment plays a crucial role in the efficacy of immunotherapy. Luo et al. identified cancer-associated fibroblasts (CAFs) that limit the effectiveness of PD-1 immunotherapy in GBM, suggesting that reprogramming the tumor immune microenvironment could enhance treatment outcomes (ref: Luo doi.org/10.1093/neuonc/). Additionally, Kim et al. explored the impact of gut microbiota dysbiosis on the immune response against brain tumors, indicating that dietary interventions may restore beneficial microbiota and improve immunotherapy efficacy (ref: Kim doi.org/10.1016/j.celrep.2025.115825/). These studies collectively emphasize the importance of both systemic and local factors in shaping the response to immunotherapy in glioblastoma patients.

The molecular landscape of neuro-oncology is rapidly evolving, with significant insights into genetic alterations and their implications for tumor behavior and treatment responses. Wilcox et al. conducted a comprehensive analysis of EGFR-mutant lung cancers with CNS metastases, revealing critical genomic drivers that contribute to CNS dissemination and treatment resistance (ref: Wilcox doi.org/10.1016/j.annonc.2025.06.001/). This study underscores the need for targeted therapies that address both systemic and CNS disease. In parallel, Drexler et al. investigated the role of cholinergic neuronal activity in promoting diffuse midline glioma growth, demonstrating that neuromodulatory signaling can influence tumor proliferation (ref: Drexler doi.org/10.1016/j.cell.2025.05.031/). These findings suggest that neuronal interactions within the tumor microenvironment may be critical for glioma progression. Furthermore, Couteau et al. explored the effects of R-2-hydroxyglutarate on telomere integrity, highlighting how metabolic alterations in gliomas can affect genomic stability (ref: Couteau doi.org/10.1093/nar/). This metabolic perspective is complemented by the establishment of Glioportal, a biobank that integrates multi-omics data to facilitate research on glioblastoma heterogeneity and therapeutic responses (ref: Pang doi.org/10.1093/neuonc/). Collectively, these studies illustrate the intricate interplay between genetic, metabolic, and environmental factors in shaping the behavior of brain tumors.

Recent clinical trials have focused on novel therapeutic strategies for brain tumors, particularly in challenging cases such as neurofibromatosis type 1 and high-risk embryonal brain tumors. Chen et al. reported on the KOMET study, which evaluated the efficacy of selumetinib in adults with symptomatic, inoperable plexiform neurofibromas, demonstrating a significant improvement in tumor response rates compared to placebo (ref: Chen doi.org/10.1016/S0140-6736(25)00986-9/). This trial highlights the potential of targeted therapies in managing complex tumor types. In pediatric populations, Mazewski et al. conducted a phase 3 trial assessing high-dose methotrexate for young children with high-risk embryonal brain tumors, finding that the addition of methotrexate significantly improved complete response rates (ref: Mazewski doi.org/10.1093/neuonc/). These findings support the integration of intensive chemotherapy regimens in pediatric neuro-oncology. Additionally, Li et al. explored high-dose aumolertinib for untreated EGFR-variant non-small cell lung cancer with brain metastases, suggesting a long-term survival benefit with a manageable safety profile (ref: Li doi.org/10.1001/jamaoncol.2025.1779/). These studies collectively emphasize the importance of innovative therapeutic approaches tailored to specific tumor characteristics and patient populations.

The tumor microenvironment (TME) plays a pivotal role in the progression and treatment response of brain tumors. Recent studies have highlighted the complex interactions between tumor cells and their surrounding environment, particularly in glioblastoma. Yu et al. developed a novel NIR-II engineered exosome nanotheranostic platform that enhances tumor targeting and penetration of the blood-brain barrier, demonstrating significant therapeutic efficacy in orthotopic glioblastoma models (ref: Yu doi.org/10.1021/acsnano.5c01541/). This innovative approach underscores the potential of nanotechnology in improving drug delivery and therapeutic outcomes in brain tumors. Moreover, Pang et al. established Glioportal, a comprehensive transcriptomic resource that elucidates ligand-mediated mesenchymal transition in glioblastoma, providing insights into the molecular mechanisms underlying tumor aggressiveness and plasticity (ref: Pang doi.org/10.1093/neuonc/). These findings emphasize the need for a deeper understanding of the TME to develop effective therapeutic strategies. Additionally, the study by Meng et al. on RIOK1 phase separation in hepatocellular carcinoma suggests that similar mechanisms may be at play in brain tumors, where stress granules could contribute to therapy resistance (ref: Meng doi.org/10.1038/s43018-025-00984-5/). Collectively, these studies highlight the intricate relationship between tumor metabolism, microenvironmental factors, and therapeutic responses in brain tumors.

Identifying reliable biomarkers and prognostic factors in neuro-oncology is crucial for improving patient outcomes. Gerstl et al. quantified Years of Life Lost (YLL) due to central nervous system tumors, revealing that glioblastoma accounts for a significant proportion of YLL among malignant CNS tumors, emphasizing its devastating impact on survival (ref: Gerstl doi.org/10.1093/neuonc/). This metric serves as a valuable tool for assessing the burden of disease and guiding resource allocation in healthcare. Additionally, Qian et al. investigated the impact of limbic white matter injury on memory performance in primary brain tumor patients, finding that specific structural changes correlated with cognitive deficits post-radiation (ref: Qian doi.org/10.1093/neuonc/). These findings suggest that neuroimaging biomarkers could be instrumental in predicting cognitive outcomes in brain tumor patients. Furthermore, Verde et al. identified cerebrospinal fluid (CSF) levels of MAP2 as a potential biomarker for amyotrophic lateral sclerosis (ALS), correlating with disease progression and survival (ref: Verde doi.org/10.1136/jnnp-2025-336208/). This highlights the importance of exploring CSF biomarkers in neuro-oncology, as they may provide insights into tumor biology and patient prognosis.

Advancements in imaging and diagnostic techniques are transforming the landscape of neuro-oncology, enabling earlier detection and improved management of brain tumors. Jiang et al. developed a deep learning system, DeepRETStroke, which utilizes retinal images to detect silent brain infarctions and predict stroke risk, showcasing the potential of non-invasive imaging modalities in neurology (ref: Jiang doi.org/10.1038/s41551-025-01413-9/). This innovative approach could facilitate early intervention and better patient outcomes. Additionally, Nia et al. introduced a method for measuring solid stress in brain tumors using intraoperative 3D navigation, providing valuable insights into the physical forces exerted by tumors on surrounding brain structures (ref: Nia doi.org/10.1158/1078-0432.CCR-24-4159/). This technique could inform surgical strategies and improve patient management. Furthermore, the integration of neoantigen vaccines with in situ cancer vaccination, as reported by Feng et al., represents a novel approach to enhance anti-tumor immunity and reshape the tumor microenvironment (ref: Feng doi.org/10.1038/s41467-025-60448-3/). These studies collectively highlight the importance of innovative imaging and diagnostic techniques in advancing neuro-oncology research and clinical practice.

Epidemiological studies in neuro-oncology provide critical insights into the burden of brain tumors and their impact on public health. Gerstl et al. quantified Years of Life Lost (YLL) due to central nervous system tumors, revealing that glioblastoma significantly contributes to premature mortality, with a total of 364,223 years lost in 2018 alone (ref: Gerstl doi.org/10.1093/neuonc/). This metric underscores the urgent need for effective prevention and treatment strategies to address the high mortality associated with these tumors. Moreover, Qian et al. examined the cognitive effects of limbic white matter injury in primary brain tumor patients, highlighting the long-term consequences of treatment on memory performance (ref: Qian doi.org/10.1093/neuonc/). Understanding these impacts is essential for developing supportive care strategies for survivors. Additionally, Jeong et al. investigated the risk of Alzheimer's disease among breast cancer survivors, finding a lower risk compared to cancer-free controls, which may inform future research on cognitive health in cancer survivors (ref: Jeong doi.org/10.1001/jamanetworkopen.2025.16468/). These findings collectively emphasize the importance of epidemiological research in shaping public health policies and improving outcomes for patients with brain tumors.