Ependymoma

This case underscores the importance of considering NF2 in young patients with simultaneous multisystem neurologic deficits, even in the absence of cutaneous stigmata. A high index of clinical suspicion, supported by multimodal imaging, is essential for early diagnosis and appropriate multidisciplinary management in such complex presentations.

It also examines therapeutic strategies targeting RCD, including recent advancements in glutathione peroxidase 4 (GPX4) inhibitors, oncolytic virotherapy, and other emerging agents. Furthermore, the review discusses the potential of nanoparticle-based drug delivery systems and multi-omics approaches to optimize personalized combination therapies, aiming to enhance multimodal, synergistic interventions for more effective glioma management.

Notably, over 80% of genes upregulated in ZFTA-RELAfus tumors were downregulated following MERTK inhibition, indicating a strong dependency on this pathway for tumor maintenance. These findings define a signaling vulnerability in ZFTA-RELA-driven ependymomas and support the clinical development of MERTK-targeted therapies for patients with the high-risk EPN-E1 subtype.

P2, N=62, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Oct 2030 --> Sep 2027 | Trial primary completion date: Oct 2029 --> Mar 2026

P1, N=70, Not yet recruiting, Robbie Majzner

They also represent the first PLAG1 fusions identified in pediatric supratentorial ependymal tumors. These cases highlight the value of integrating histology, methylation profiling, and fusion detection, and suggest a new candidate supratentorial ependymal subtype with PLAG1 fusions, pending validation in larger series.

Taken together, our results position itaconate upregulation as a previously unappreciated driver of ZFTA-RELA+ ependymomas. Our work has implications for future drug development to reduce pathogenic ZFTA-RELA expression for this brain tumour, and will advance our understanding of oncometabolites as a new class of therapeutic dependencies in cancers.

Remarkably, normalizing hematopoiesis with a single infusion of antibodies directed against cytokines enriched in the cerebrospinal fluid of mice bearing ZFTA-RELA ependymomas, choroid plexus carcinomas or group 3 medulloblastoma-all aggressive childhood brain tumors-disrupted this process and caused profound tumor regression. These findings demonstrate the existence of a skull bone marrow-tumor immunological interface and suggest that modulating the local supply of myeloid cells could represent a less toxic therapeutic strategy for aggressive childhood brain tumors.

Supratentorial ependymomas with ZFTA-RELA fusions represent a highly aggressive pediatric brain tumor subtype, yet the post-transcriptional mechanisms driving their malignancy remain unclear. This study fills a critical gap by systematically profiling miRNA expression in fusion-positive and fusion-negative supratentorial ependymomas, revealing a distinct fusion-associated miRNA signature. The identification of hsa-miR-138-5p upregulation and hsa-miR-135b-5p/hsa-miR-216a-3p downregulation, converging on key oncogenic nodes such as TERT, YAP1, RELA, and TP53, provides novel mechanistic insight into how fusion-driven miRNA dysregulation enhances epithelial-mesenchymal transition and stemness. The findings suggest that miRNA-fusion interactions play an important role in tumor aggressiveness and highlight hsa-miR-138-5p as a potential biomarker for disease progression. Clinically, the work advances understanding of fusion-driven ependymoma biology and lays the foundation for developing miRNA-based diagnostic and therapeutic strategies targeting molecular mechanisms of tumor progression.

P=N/A, N=94, Recruiting, Tata Memorial Centre | Phase classification: P3 --> P=N/A

P1/2, N=63, Active, not recruiting, Centre Oscar Lambret | Trial primary completion date: May 2025 --> Dec 2025

P1, N=71, Active, not recruiting, National Cancer Institute (NCI) | N=110 --> 71 | Trial completion date: Dec 2025 --> Jan 2027