Recent studies have elucidated critical molecular mechanisms underlying gliomas and neurodevelopmental tumors, particularly focusing on the genetic and epigenetic alterations that drive tumorigenesis. Liu et al. identified that diffuse hemispheric gliomas with H3G34 mutations originate from interneuronal precursors, revealing a cellular hierarchy that mirrors human brain development. This study emphasizes the potential for targeting these developmental pathways for therapeutic interventions (ref: Liu doi.org/10.1016/j.ccell.2024.08.006/). In a complementary approach, Lee et al. conducted a high-throughput screening of neuroactive drugs, discovering several repurposable compounds with potent anti-glioblastoma activity, highlighting the importance of exploring neurophysiological vulnerabilities in glioblastoma treatment (ref: Lee doi.org/10.1038/s41591-024-03224-y/). Furthermore, Massimino et al. investigated the long-term outcomes of a hyperfractionated radiotherapy strategy for high-risk medulloblastoma, demonstrating that molecular subtypes significantly influence treatment efficacy and patient prognosis (ref: Massimino doi.org/10.1093/neuonc/). Concurrently, Lee et al. described a subset of neuroepithelial tumors with EWSR1-PLAGL1 rearrangements, revealing concurrent ependymal and ganglionic differentiation, which may inform future diagnostic and therapeutic strategies (ref: Lee doi.org/10.1186/s40478-024-01809-9/). Lastly, Jurmeister et al. provided a comprehensive DNA methylation profiling of salivary gland tumors, offering insights into their classification and potential therapeutic targets (ref: Jurmeister doi.org/10.1016/j.modpat.2024.100625/).

The exploration of biomarkers in neuropathology has gained momentum, particularly with the application of advanced sequencing techniques and metabolomic profiling. Menzel et al. benchmarked whole exome sequencing (WES) across multiple centers, demonstrating its efficacy in identifying somatic and germline variants in cancer diagnostics, thus broadening the scope of personalized medicine (ref: Menzel doi.org/10.1016/j.ejca.2024.114306/). In a related study, Möhn et al. analyzed cerebrospinal fluid (CSF) metabolomic profiles in glioma patients, revealing significant differences compared to controls, which correlated with established glioma diagnostic markers (ref: Möhn doi.org/10.1007/s00415-024-12667-9/). Additionally, Pollaci et al. investigated CSF and plasma biomarkers in patients with iatrogenic cerebral amyloid angiopathy, highlighting the need for biomarker analysis in differentiating between sporadic and iatrogenic cases (ref: Pollaci doi.org/10.1212/WNL.0000000000209828/). Spitz et al. examined plasma biomarkers in chronic traumatic brain injury, finding associations with cognitive decline and white matter microstructure, thus emphasizing the potential for plasma biomarkers in monitoring TBI outcomes (ref: Spitz doi.org/10.1093/brain/). Lastly, Quiring et al. focused on the epigenetic characteristics of glioblastoma, revealing that these features may vary during disease progression and influence clinical outcomes (ref: Quiring doi.org/10.3390/biomedicines12092078/).

Genetic and epigenetic factors play a pivotal role in the pathogenesis of various neurological disorders, as evidenced by recent findings in rhabdoid tumors and progressive supranuclear palsy (PSP). Fleischmann et al. reported constitutional mosaicism of pathogenic SMARCB1 variants in sporadic rhabdoid tumors, suggesting that this genetic alteration may be more common than previously recognized (ref: Fleischmann doi.org/10.1093/neuonc/). In a separate investigation, Farrell et al. conducted a comprehensive analysis of PSP, implicating glial activation and identifying novel risk genes that may contribute to the disease's unique pathology, which differs from other neurodegenerative disorders (ref: Farrell doi.org/10.1038/s41467-024-52025-x/). Kemps et al. explored recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma, highlighting the genetic landscape of this histiocytic neoplasm and its clinical implications (ref: Kemps doi.org/10.1182/blood.2024025127/). Additionally, Cyrta et al. expanded the understanding of tumors with SMARCA2/4::CREM fusions, emphasizing the need for integrated genomic assessments in tumor classification (ref: Cyrta doi.org/10.1002/path.6350/). Lastly, Masui et al. addressed the challenges of incorporating molecular diagnostics into routine assessments of IDH-mutant astrocytomas, underscoring the importance of genetic markers in determining malignancy and prognosis (ref: Masui doi.org/10.1111/neup.13005/).

Neuroinflammation and neurodegeneration are closely intertwined processes that significantly impact cognitive function and disease progression in conditions such as Alzheimer's disease and multiple sclerosis. Zatcepin et al. investigated the regional desynchronization of microglial activity in Alzheimer's disease, proposing a microglia connectome as a potential biomarker for cognitive decline (ref: Zatcepin doi.org/10.1186/s13024-024-00752-6/). In a related study, Bergner et al. highlighted the role of BCAS1-positive oligodendrocytes in remyelination processes in multiple sclerosis, suggesting that the differentiation of these cells is crucial for recovery from demyelination (ref: Bergner doi.org/10.1093/brain/). Li et al. explored the therapeutic potential of in vivo self-assembled siRNA in Machado-Joseph disease, demonstrating a novel approach to target the mutant ATXN3 protein responsible for this hereditary ataxia (ref: Li doi.org/10.1093/brain/). Furthermore, Ma et al. reported that chronic noise exposure induces Alzheimer's disease-like neuropathology and cognitive impairment in rats, implicating ferroptosis as a mechanism underlying these changes (ref: Ma doi.org/10.1265/ehpm.24-00126/). Collectively, these studies underscore the importance of understanding neuroinflammatory processes and their implications for therapeutic strategies in neurodegenerative diseases.

The search for effective therapeutic strategies and drug repurposing has gained traction, particularly in the context of complex diseases such as glioblastoma and other malignancies. Lee et al. conducted a high-throughput identification of neuroactive drugs with anti-glioblastoma activity, revealing promising candidates that could be repurposed for clinical use, thus addressing the urgent need for novel treatment options in this aggressive cancer (ref: Lee doi.org/10.1038/s41591-024-03224-y/). In a related effort, Li et al. developed a polypharmacological drug design approach that integrates phenotypic and restricted fragment docking strategies, aiming to create multitarget drugs that can effectively treat complex diseases (ref: Li doi.org/10.1021/acs.jmedchem.4c01731/). Andolfi et al. explored the modulation of androgen receptor activity in prostate cancer, demonstrating that inhibiting MED12 and CDK8/19 can enhance the efficacy of enzalutamide, a common therapeutic agent (ref: Andolfi doi.org/10.1210/endocr/). Additionally, Kemps et al. provided insights into juvenile xanthogranuloma, emphasizing the importance of understanding genetic alterations in guiding treatment decisions (ref: Kemps doi.org/10.1182/blood.2024025127/). These studies collectively highlight the potential of drug repurposing and innovative therapeutic strategies in improving clinical outcomes across various malignancies.

Clinical outcomes and prognostic factors in central nervous system (CNS) tumors are critical for guiding treatment strategies and improving patient survival. Massimino et al. evaluated the long-term outcomes of a hyperfractionated accelerated radiotherapy strategy for high-risk medulloblastoma, revealing that molecular subtypes significantly influence treatment response and overall prognosis (ref: Massimino doi.org/10.1093/neuonc/). An et al. identified several factors associated with central nervous system dissemination in spinal cord astrocytomas, including H3 K27M mutations and higher histopathological grades, which correlated with poorer survival outcomes (ref: An doi.org/10.3171/2024.6.SPINE24233/). Lenga et al. conducted a retrospective analysis of pediatric spinal tumors, providing valuable insights into their etiology, clinical presentation, and treatment outcomes, which are essential for improving management strategies in this vulnerable population (ref: Lenga doi.org/10.1007/s10143-024-02770-w/). McNeilly et al. investigated the role of collagen IV deficiency in small vessel disease, linking genetic variants to vascular dysfunction and intracerebral hemorrhage, thereby shedding light on the underlying mechanisms of these conditions (ref: McNeilly doi.org/10.1016/j.ebiom.2024.105315/). Collectively, these studies underscore the importance of understanding clinical outcomes and prognostic factors in CNS tumors to enhance patient care and treatment efficacy.

Emerging tumor entities and their associated genetic alterations are reshaping our understanding of cancer biology and classification. Stellingwerff et al. demonstrated that quantitative MRI can distinguish between different leukodystrophies, correlating imaging findings with clinical measures, which may aid in the diagnosis and management of these rare conditions (ref: Stellingwerff doi.org/10.1007/s00330-024-11089-5/). Cyrta et al. expanded the clinicopathologic spectrum of tumors with SMARCA2/4::CREM fusions, highlighting the diverse neoplasms associated with these genetic alterations and their implications for diagnosis and treatment (ref: Cyrta doi.org/10.1002/path.6350/). Masui et al. emphasized the need for integrated assessments of malignancy in IDH-mutant astrocytomas, advocating for the incorporation of molecular diagnostics into routine practice to improve prognostic accuracy (ref: Masui doi.org/10.1111/neup.13005/). These findings collectively underscore the importance of recognizing emerging tumor entities and their genetic underpinnings to enhance diagnostic precision and therapeutic strategies in oncology.