Recent advancements in molecular and genetic research have significantly enhanced our understanding of neuro-oncology, particularly in the context of gliomas and medulloblastomas. Tedesco et al. introduced a novel single-cell method, scGET-seq, which allows for comprehensive profiling of both open and closed chromatin, revealing genetic events that contribute to cancer drug resistance in cancer-derived organoids and patient-derived xenograft models (ref: Tedesco doi.org/10.1038/s41587-021-01031-1/). In parallel, Liu et al. and Prensner et al. highlighted the clinical utility of cell-free DNA from cerebrospinal fluid as a biomarker for measurable residual disease (MRD) in medulloblastoma, demonstrating its potential in monitoring treatment response and improving prognostic assessments (ref: Liu doi.org/10.1016/j.ccell.2021.09.012/; Prensner doi.org/10.1016/j.ccell.2021.09.014/). Johnson et al. and Chaligne et al. further explored glioma heterogeneity, identifying epigenetic regulators and transcriptional cell state diversity that contribute to therapeutic resistance, emphasizing the role of local DNA methylation disorders in aggressive tumor behavior (ref: Johnson doi.org/10.1038/s41588-021-00926-8/; Chaligne doi.org/10.1038/s41588-021-00927-7/). Additionally, Faas et al. investigated the metabolic reprogramming of alternatively activated macrophages, linking IL-33 signaling to inflammation resolution, which may have implications for the tumor microenvironment (ref: Faas doi.org/10.1016/j.immuni.2021.09.010/). Lastly, Yang et al. demonstrated that glucosylated polymer chains conjugated to checkpoint blockade antibodies enhance their efficacy against glioblastoma, suggesting a promising therapeutic strategy to overcome the challenges posed by the blood-tumor barrier (ref: Yang doi.org/10.1038/s41551-021-00803-z/).

The integration of advanced imaging techniques and biomarker analysis has revolutionized the diagnosis and treatment of brain tumors. Shi et al. introduced Raman dye imaging and tissue clearing (RADIANT), a method that allows for highly multiplexed volumetric mapping of proteins in thick tissue samples, significantly enhancing the visualization of tumor microenvironments (ref: Shi doi.org/10.1038/s41587-021-01041-z/). Maas et al. developed an integrated molecular-morphologic classification system for meningiomas, which improved diagnostic accuracy and risk stratification, outperforming traditional WHO grading systems (ref: Maas doi.org/10.1200/JCO.21.00784/). Hu et al. presented SpaGCN, a graph convolutional network approach that combines gene expression data with spatial location and histology, facilitating the identification of spatially variable genes in tumor tissues (ref: Hu doi.org/10.1038/s41592-021-01255-8/). Furthermore, Furtner et al. explored the prognostic significance of temporal muscle thickness in glioblastoma patients, linking it to skeletal muscle status and potential treatment outcomes (ref: Furtner doi.org/10.1158/1078-0432.CCR-21-1987/). Cluceru et al. demonstrated the potential of deep learning and diffusion-weighted imaging to classify glioma genetic subtypes noninvasively, highlighting the importance of integrating imaging with molecular data for improved diagnostic precision (ref: Cluceru doi.org/10.1093/neuonc/).

Innovative therapeutic strategies are being developed to enhance treatment efficacy and safety in neuro-oncology. Yang et al. demonstrated that conjugating glucosylated polymer chains to checkpoint blockade antibodies significantly improves their specificity and efficacy against glioblastoma, suggesting a promising approach to mitigate immune-related adverse events (ref: Yang doi.org/10.1038/s41551-021-00803-z/). Liu et al. and Prensner et al. highlighted the use of cell-free DNA in cerebrospinal fluid as a biomarker for measurable residual disease in medulloblastoma, which could guide treatment decisions and improve patient outcomes (ref: Liu doi.org/10.1016/j.ccell.2021.09.012/; Prensner doi.org/10.1016/j.ccell.2021.09.014/). Ogunnaike et al. explored the use of fibrin gel to enhance the delivery and efficacy of CAR T cells in glioblastoma, demonstrating superior antitumor activity compared to traditional methods (ref: Ogunnaike doi.org/10.1126/sciadv.abg5841/). Additionally, Wang et al. investigated the role of MET overexpression in glioblastoma, linking it to immunosuppressive signaling pathways that could be targeted for therapeutic intervention (ref: Wang doi.org/10.1136/jitc-2021-002451/). Jan et al. presented a novel approach using CAR-NK cells targeting HLA-G to convert immunosuppression into effective tumor ablation, indicating a potential strategy for overcoming the challenges of solid tumors (ref: Jan doi.org/10.1136/jitc-2021-003050/).

Clinical outcomes in neuro-oncology are increasingly being linked to specific treatment responses and patient characteristics. Acharya et al. investigated the relationship between radiation dose to critical brain structures and neurocognitive outcomes in children with medulloblastoma, emphasizing the need for substructure-informed planning to minimize cognitive deficits (ref: Acharya doi.org/10.1200/JCO.21.01480/). Hirsch et al. assessed the efficacy of cabozantinib for treating brain metastases in renal cell carcinoma, reporting significant response rates and survival outcomes, thus supporting its use in this patient population (ref: Hirsch doi.org/10.1001/jamaoncol.2021.4544/). Maas et al. further validated an integrated molecular-morphologic classification for meningiomas, which improved prognostic accuracy across multiple cohorts (ref: Maas doi.org/10.1200/JCO.21.00784/). Furtner et al. also highlighted the prognostic relevance of temporal muscle thickness in glioblastoma patients, linking it to sarcopenia and adverse outcomes (ref: Furtner doi.org/10.1158/1078-0432.CCR-21-1987/). Additionally, Ordureau et al. provided insights into proteome remodeling during neurogenesis, which may have implications for understanding treatment responses in neuro-oncology (ref: Ordureau doi.org/10.1016/j.molcel.2021.10.001/).

The tumor microenvironment plays a crucial role in shaping immune responses in neuro-oncology. Wang et al. explored the impact of MET overexpression on PD-L1 signaling and macrophage-mediated immunosuppression in glioblastomas, suggesting that targeting this pathway could enhance therapeutic efficacy (ref: Wang doi.org/10.1136/jitc-2021-002451/). Jan et al. investigated the use of CAR-NK cells targeting HLA-G to overcome immunosuppression in solid tumors, demonstrating promising results in tumor ablation both in vitro and in vivo (ref: Jan doi.org/10.1136/jitc-2021-003050/). Lau et al. examined the resistance mechanisms to ipilimumab-nivolumab in melanoma brain metastases, revealing low response rates and highlighting the need for alternative strategies in this context (ref: Lau doi.org/10.1136/jitc-2021-002995/). Ogunnaike et al. developed a fibrin gel to enhance CAR T cell delivery in glioblastoma, showing improved antitumor activity compared to traditional methods (ref: Ogunnaike doi.org/10.1126/sciadv.abg5841/). Furtner et al. also linked temporal muscle thickness to immune status in glioblastoma patients, suggesting that muscle health may influence treatment outcomes (ref: Furtner doi.org/10.1158/1078-0432.CCR-21-1987/).

Epidemiological studies in neuro-oncology provide critical insights into tumor incidence, survival rates, and treatment outcomes. The CBTRUS Statistical Report highlighted that the average annual age-adjusted incidence rate for malignant and non-malignant brain tumors was 24.25, with a five-year relative survival rate of 66.9% for malignant tumors (ref: Ostrom doi.org/10.1093/neuonc/). Hoogstrate et al. conducted a meta-omics analysis of the EGFRvIII transcriptome in glioblastoma, revealing conflicting prognostic implications and underscoring the need for further investigation into its role in tumor biology (ref: Hoogstrate doi.org/10.1093/neuonc/). Park et al. characterized temozolomide-induced aplastic anemia in CNS malignancies, providing valuable data on prognosis and treatment challenges associated with this rare complication (ref: Park doi.org/10.1093/neuonc/). Panwalkar et al. focused on targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas, emphasizing the need for tailored therapeutic approaches in this high-risk population (ref: Panwalkar doi.org/10.1126/scitranslmed.abc0497/). Lastly, Lau et al. examined the resistance of melanoma brain metastases to immunotherapy, highlighting the need for innovative strategies to improve patient outcomes (ref: Lau doi.org/10.1136/jitc-2021-002995/).

Guidelines and standards in neuro-oncology are essential for improving diagnosis and treatment protocols. Nakamura et al. provided comprehensive guidelines for the diagnosis and treatment of central nervous system germ cell tumors, emphasizing the importance of histopathological examination and the limited role of surgery (ref: Nakamura doi.org/10.1093/neuonc/). Brastianos et al. conducted a Phase II study on the efficacy of ipilimumab and nivolumab in leptomeningeal carcinomatosis, presenting valuable data on overall survival and treatment tolerability (ref: Brastianos doi.org/10.1038/s41467-021-25859-y/). Prakadan et al. explored genomic and transcriptomic correlates of immunotherapy response in leptomeningeal metastases, highlighting the potential for personalized treatment approaches (ref: Prakadan doi.org/10.1038/s41467-021-25860-5/). Furtner et al. also contributed to the understanding of prognostic markers in glioblastoma, linking temporal muscle thickness to treatment outcomes and sarcopenia risk (ref: Furtner doi.org/10.1158/1078-0432.CCR-21-1987/). These studies collectively underscore the importance of integrating clinical guidelines with emerging research to enhance patient care in neuro-oncology.