The tumor microenvironment plays a critical role in the immune evasion of glioblastoma multiforme (GBM). Gangoso et al. demonstrated that glioblastoma stem cells (GSCs) acquire myeloid-affiliated transcriptional programs through epigenetic immunoediting, allowing them to establish an immunosuppressive microenvironment that facilitates immune escape (ref: Gangoso doi.org/10.1016/j.cell.2021.03.023/). This finding highlights the dynamic nature of GSCs and their ability to adapt to host immune responses. Additionally, Randles et al. utilized computational modeling to explore the spatiotemporal dynamics of the perivascular niche in glioblastoma, revealing that GSCs can transition between chemoradiation-resistant and sensitive states. Their model suggests that optimizing treatment schedules for concurrent radiation and temozolomide could enhance therapeutic efficacy (ref: Randles doi.org/10.1038/s41551-021-00710-3/). Furthermore, Zhang et al. introduced bradykinin aggregation-induced-emission nanoparticles that enhance photothermal therapy by improving penetration through the blood-tumor barrier, potentially inducing local immune responses against GBM (ref: Zhang doi.org/10.1002/adma.202008802/). These studies collectively underscore the complexity of the tumor microenvironment in GBM and the need for innovative therapeutic strategies to overcome immune evasion.

Innovative treatment strategies are crucial for improving outcomes in patients with high-grade gliomas. Friedman et al. conducted a phase 1 trial of oncolytic HSV-1 G207 immunovirotherapy in pediatric patients, demonstrating an acceptable safety profile and evidence of clinical responses in recurrent or progressive high-grade gliomas (ref: Friedman doi.org/10.1056/NEJMoa2024947/). This approach highlights the potential of virotherapy as a novel treatment modality. In parallel, Bowers et al. emphasized the importance of surveillance for subsequent CNS neoplasms in childhood cancer survivors, advocating for early diagnosis and intervention to enhance long-term health outcomes (ref: Bowers doi.org/10.1016/S1470-2045(20)30688-4/). Additionally, Lee et al. introduced a precision oncology framework called SELECT, which leverages tumor transcriptome data to predict patient responses to therapy, thereby expanding treatment options for glioblastoma patients (ref: Lee doi.org/10.1016/j.cell.2021.03.030/). These studies collectively illustrate the ongoing efforts to develop innovative therapies and improve patient management in neuro-oncology.

Understanding the molecular mechanisms underlying glioblastoma is essential for identifying potential biomarkers and therapeutic targets. Maiani et al. revealed that AMBRA1 regulates cyclin D to maintain genomic integrity and proper cell cycle progression, highlighting its role in cancer biology (ref: Maiani doi.org/10.1038/s41586-021-03422-5/). Furthermore, Volmar et al. demonstrated that cannabidiol can convert NF-κB into a tumor suppressor in glioblastoma, suggesting a novel therapeutic strategy to modulate oncogenic signaling pathways (ref: Volmar doi.org/10.1093/neuonc/). In addition, Marner et al. assessed the diagnostic accuracy of [18F]FET PET in pediatric CNS tumors, finding that it significantly aids in differentiating tumor from non-tumor lesions, thereby enhancing clinical decision-making (ref: Marner doi.org/10.1093/neuonc/). These findings underscore the importance of molecular insights and imaging techniques in advancing glioblastoma research and treatment.

Genetic and epigenetic factors significantly influence the development and progression of brain tumors. Li et al. explored the role of PI3Kγ inhibition in glioblastoma, demonstrating that it suppresses microglia and tumor-associated macrophage accumulation, thereby enhancing the response to temozolomide in murine models (ref: Li doi.org/10.1073/pnas.2009290118/). This study highlights the potential of targeting the tumor microenvironment to improve therapeutic outcomes. Additionally, Brooks et al. identified the white matter as a pro-differentiative niche for glioblastoma, where tumor cell differentiation is driven by SOX10 upregulation, suggesting a complex interplay between tumor biology and the surrounding neural tissue (ref: Brooks doi.org/10.1038/s41467-021-22225-w/). Furthermore, Bowers et al. provided guidelines for surveillance of subsequent CNS neoplasms in childhood cancer survivors, emphasizing the need for monitoring genetic predispositions and treatment-related risks (ref: Bowers doi.org/10.1016/S1470-2045(20)30688-4/). These studies collectively illustrate the intricate genetic and epigenetic landscape of brain tumors and its implications for patient management.

Research on neurodevelopmental and pediatric tumors highlights the unique challenges faced in treating these conditions. Frappaz et al. conducted a phase I/II trial of vismodegib combined with temozolomide for recurrent medulloblastoma, but the study was prematurely terminated due to insufficient progression-free survival rates (ref: Frappaz doi.org/10.1093/neuonc/). This underscores the need for more effective treatment strategies in pediatric populations. Khan et al. investigated postoperative posterior fossa syndrome, finding that severe ataxia and movement disorders were common, with older age and high ataxia scores associated with delayed recovery (ref: Khan doi.org/10.1093/neuonc/). Additionally, Bowers et al. emphasized the importance of surveillance for subsequent CNS neoplasms in childhood cancer survivors, advocating for proactive monitoring to improve long-term health outcomes (ref: Bowers doi.org/10.1016/S1470-2045(20)30688-4/). These findings highlight the complexities of managing pediatric brain tumors and the necessity for tailored approaches.

Clinical outcomes and patient management strategies are critical in the context of glioblastoma treatment. Gangoso et al. explored the mechanisms of immune evasion in GBM, revealing that GSCs can adapt to establish an immunosuppressive environment, complicating treatment efforts (ref: Gangoso doi.org/10.1016/j.cell.2021.03.023/). Randles et al. developed a computational model to optimize treatment schedules for glioblastoma, demonstrating that understanding the dynamics of the tumor microenvironment can enhance therapeutic efficacy (ref: Randles doi.org/10.1038/s41551-021-00710-3/). Furthermore, Viswanath et al. utilized metabolic imaging to assess TERT expression in low-grade gliomas, providing insights into tumor biology and potential biomarkers for treatment response (ref: Viswanath doi.org/10.1093/neuonc/). These studies collectively emphasize the importance of integrating clinical insights with innovative methodologies to improve patient management in glioblastoma.

Neuro-oncology research methodologies are evolving to address the complexities of brain tumors. Gangoso et al. highlighted the role of GSCs in immune evasion, emphasizing the need for innovative research approaches to understand tumor biology (ref: Gangoso doi.org/10.1016/j.cell.2021.03.023/). Randles et al. employed computational modeling to analyze the dynamics of the glioblastoma microenvironment, demonstrating its utility in optimizing treatment regimens (ref: Randles doi.org/10.1038/s41551-021-00710-3/). Additionally, Viswanath et al. utilized metabolic imaging to investigate TERT expression in low-grade gliomas, showcasing the potential of advanced imaging techniques in neuro-oncology research (ref: Viswanath doi.org/10.1093/neuonc/). These methodologies reflect a shift towards integrating computational and imaging technologies to enhance our understanding of brain tumors and improve therapeutic strategies.