Neurooncology: 2025 update

Abstract

This collection of studies highlights groundbreaking advancements in brain tumor research, particularly primary CNS tumors and brain metastasis. One major focus is the tumor microenvironment, where alterations in cerebral microcirculation and hypoxic-ischemic conditions have been shown to influence metastatic progression. In glioblastoma, recurrent tumors exhibit distinct DNA methylation profiles, and global DNA methylation has emerged as an independent diagnostic marker for IDH-wildtype glioblastoma. A whole-tumor perspective further emphasizes the extensive intratumoral heterogeneity driving glioblastoma evolution. The immune landscape of glioblastoma is another key area of research. Cranioencephalic functional lymphoid units have been implicated in tumor progression, while time-dependent single-cell phenotyping offers novel insights into immune cell dynamics within glioblastoma. Additionally, histone serotonylation has been identified as a critical epigenetic regulator in ependymoma tumorigenesis. Diagnostic and prognostic innovations are paving the way for improved patient care. Histomorphological features provide enhanced prognosis prediction for glioblastoma patients. Confocal laser microscopy enables real-time intraoperative histopathological diagnostics, and sequencing of cerebrospinal fluid-derived cell-free DNA presents a promising non-invasive diagnostic approach. Together, these top studies of 2024 underscore the complexity of brain tumor biology and the integration of epigenetics, immune interactions, and advanced diagnostics into clinical practice. These insights mark significant progress toward personalized treatment strategies and improved outcomes in neurooncology.

Keywords: Brain metastasis; Brain tumors; Glioblastoma; Neurooncology; Neuropathology.

Figure 1: Concept of brain metastasis formation and therapeutic prevention

Figure 2: Risk stratification for IDH wildtype glioblastoma patients.

Patient age over 65 years, extent of less than 90 % of the contrast-enhancing tumor area, an unmethylated MGMT promoter and a low mean global methylation beta value of less than 0.49 are considered as negative prognostic factors. Median overall survival times are as follows: risk group 1: 39 months; risk group 2: 19 months; risk group 3: 8.3 months.

Figure 3: Temporal molecular change between primary and recurrent glioblastoma

Figure 4: 3D glioblastoma evolution and heterogeneity: methodological approach and key findings.

Abbreviations: oRG: outer radial glia; IPC: intermediate progenitor cell; OPC: oligodendrocyte precursor cell; NEUROD1: neuronal differentiation 1 (transcription factor); AP-1: activator protein 1 (transcription factor).

Figure 5: Cranioencephalic functional lymphoid units in glioblastoma.

Left side: methodological set-up. Right side: major findings according to compartment.

Figure 6: Prognostic prediction of histological features in glioblastoma

Figure 7

Diagnostic set-up and major results for clinical phase II non-inferiority study for intraoperative neuropathological assessment using fluorescein-stained confocal laser endomicroscopy.

Figure 8: Time-dependent immune cells transcriptomics in glioblastoma.

Left side: methodological set-up. Right side: major findings of NK and myeloid cell/TAM transcriptional trajectories.

Figure 9: Disparate effects of serotonin in ependymoma tumorigenesis.

On the one hand, serotonin signaling from the dorsal raphe nucleus inhibits remote ependymoma growth, most likely by reducing neuronal activity in the tumor microenvironment. On the other hand, tumor cell-intrinsic serotonylation promotes ependymoma growth through epigenetic modification and subsequent ETV5 overexpression, ultimately leading to neuropeptide Y (NPY) inhibition. As a result, the inhibitory effect of NPY on brain activity and its tumor-suppressive function are abolished.