Recent studies have elucidated various molecular mechanisms contributing to glioma malignancy, particularly focusing on the role of the Kyn-AhR-AQP4 signaling pathway. Du et al. demonstrated that the expression and activity of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) were positively correlated with glioma pathologic grades, Ki67 index, and overall survival, suggesting their potential involvement in glioma cell motility through aquaporin 4 (AQP4) expression (ref: Du doi.org/10.1038/s41392-019-0103-4/). In pediatric low-grade gliomas (pLGGs), Ryall et al. analyzed over 1,000 cases and found that 84% harbored driver alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway, highlighting the genetic underpinnings of these tumors and the variability in clinical outcomes (ref: Ryall doi.org/10.1016/j.ccell.2020.03.011/). Furthermore, Xu et al. explored the role of the gluconeogenic enzyme PCK1 in phosphorylating INSIG1/2, which is crucial for lipogenesis in cancer cells, indicating a metabolic adaptation that supports glioma proliferation (ref: Xu doi.org/10.1038/s41586-020-2183-2/). These findings collectively underscore the intricate molecular landscape of gliomas, revealing potential therapeutic targets and the need for further investigation into metabolic pathways that facilitate tumor growth.

The immune landscape in neuro-oncology has been significantly impacted by recent advancements in immunotherapy, particularly in the context of glioblastoma and medulloblastoma. Maier et al. identified a conserved dendritic-cell regulatory program that limits antitumor immunity, emphasizing the role of conventional type 1 dendritic cells (DC1s) in enhancing responses to checkpoint blockade therapies (ref: Maier doi.org/10.1038/s41586-020-2134-y/). In a promising approach, Donovan et al. validated the intrathecal delivery of CAR T cells targeting EPHA2, HER2, and IL13Rα2 for treating metastatic medulloblastoma and ependymoma in mouse models, demonstrating significant therapeutic efficacy (ref: Donovan doi.org/10.1038/s41591-020-0827-2/). Additionally, Bayik et al. explored the role of myeloid-derived suppressor cell subsets in glioblastoma, revealing sex-specific differences in their contributions to tumor growth, which could inform tailored immunotherapeutic strategies (ref: Bayik doi.org/10.1158/2159-8290.CD-19-1355/). These studies highlight the complexity of the immune response in neuro-oncology and the potential for innovative immunotherapeutic interventions.

Clinical trials continue to shape the landscape of treatment strategies for gliomas, with a focus on differentiating between treatment-induced effects and tumor recurrence. Cluceru et al. investigated the magnetic resonance (MR) signatures of recurrent tumors and treatment effects, finding that a cutoff value of 2.7 for the contrast normalization index (CNI) provided a sensitivity of 0.61 and specificity of 0.81 in distinguishing between these two conditions (ref: Cluceru doi.org/10.1093/neuonc/). The 'Head Start' III trial, led by Dhall et al., reported excellent outcomes for young children with nodular desmoplastic medulloblastoma treated with intensive chemotherapy and autologous hematopoietic cell rescue, suggesting a shift away from craniospinal irradiation in this population (ref: Dhall doi.org/10.1093/neuonc/). Furthermore, the OPARATIC trial assessed the pharmacokinetics and safety of olaparib in recurrent glioblastoma, revealing challenges in brain penetration and the need for further exploration of combination therapies (ref: Hanna doi.org/10.1093/neuonc/). These findings underscore the importance of refining treatment protocols and understanding the nuances of glioma management.

Technological innovations are revolutionizing glioma research, particularly in imaging and targeted therapies. Dong et al. developed a deep learning radiomic nomogram for predicting lymph node metastasis in gastric cancer, showcasing the potential of artificial intelligence in enhancing diagnostic accuracy (ref: Dong doi.org/10.1016/j.annonc.2020.04.003/). Li et al. introduced carbon quantum dots that selectively target tumors by mimicking large amino acids, facilitating both imaging and drug delivery in glioma models, thus paving the way for more effective theranostic approaches (ref: Li doi.org/10.1038/s41551-020-0540-y/). Additionally, Liu et al. utilized CRISPRi technology to identify long non-coding RNAs as potential therapeutic targets in glioma, highlighting the role of epigenetic factors in cancer treatment (ref: Liu doi.org/10.1186/s13059-020-01995-4/). These advancements not only enhance our understanding of glioma biology but also open new avenues for precision medicine.

Genetic and epigenetic factors play a crucial role in the pathogenesis of gliomas, influencing both diagnosis and treatment outcomes. Ullrich et al. conducted a phase II study on the mTOR inhibitor everolimus for treating NF1-associated pediatric low-grade gliomas, revealing its potential efficacy in this specific patient population (ref: Ullrich doi.org/10.1093/neuonc/). Fukuoka et al. emphasized the importance of combined epigenetic and molecular analyses in pediatric low-grade gliomas, demonstrating how methylation profiling can enhance prognostic accuracy (ref: Fukuoka doi.org/10.1093/neuonc/). Moreover, Dahl et al. identified the Super Elongation Complex as a targetable dependency in diffuse midline gliomas, suggesting that targeting epigenetic dysregulation could provide new therapeutic strategies (ref: Dahl doi.org/10.1016/j.celrep.2020.03.049/). These studies highlight the intricate interplay between genetic alterations and epigenetic modifications in glioma progression and treatment response.

The tumor microenvironment significantly influences glioma progression and treatment response. Pine et al. demonstrated that a neuroanatomically accurate human microenvironment is critical for maintaining cellular states found in primary glioblastomas, suggesting that current models may not fully recapitulate tumor biology (ref: Pine doi.org/10.1158/2159-8290.CD-20-0057/). Sarkar et al. explored the potential of niacin to reactivate myeloid cells in glioblastoma, proposing a novel therapeutic strategy to enhance antitumor immunity by targeting the tumor microenvironment (ref: Sarkar doi.org/10.1126/scitranslmed.aay9924/). Additionally, Montgomery et al. investigated glioma-induced alterations in neuronal activity and neurovascular coupling, revealing how these changes contribute to disease progression and neurological complications (ref: Montgomery doi.org/10.1016/j.celrep.2020.03.064/). These findings underscore the importance of the tumor microenvironment in glioma biology and the potential for therapeutic interventions that target these interactions.

The COVID-19 pandemic has posed unique challenges for neuro-oncology, particularly in the management of glioma patients. Mohile et al. highlighted the urgent considerations for treating glioma patients during the pandemic, emphasizing the vulnerability of this population due to age and immunosuppression (ref: Mohile doi.org/10.1093/neuonc/). Tabrizi et al. developed a quantitative framework to model COVID-19 risk during adjuvant therapy for glioblastoma, providing insights into the potential impact of the pandemic on treatment outcomes (ref: Tabrizi doi.org/10.1093/neuonc/). Furthermore, Guida et al. discussed strategies to prevent or remediate cancer and treatment-related aging, which have become increasingly relevant as cancer survivors face compounded risks during the pandemic (ref: Guida doi.org/10.1093/jnci/). These studies underscore the need for adaptive strategies in neuro-oncology to navigate the complexities introduced by the COVID-19 crisis.

Pediatric neuro-oncology has seen significant advancements in understanding and treating brain tumors, particularly low-grade gliomas. Ullrich et al. conducted a phase II study on the mTOR inhibitor everolimus for recurrent NF1-associated pediatric low-grade gliomas, demonstrating its potential efficacy in this specific cohort (ref: Ullrich doi.org/10.1093/neuonc/). Li et al. explored targeted tumor theranostics using carbon quantum dots, which selectively accumulate in glioma models, enhancing imaging and therapeutic delivery (ref: Li doi.org/10.1038/s41551-020-0540-y/). Fukuoka et al. emphasized the clinical impact of combined epigenetic and molecular analysis in pediatric low-grade gliomas, highlighting the importance of integrating genetic and methylation profiling for improved prognostic outcomes (ref: Fukuoka doi.org/10.1093/neuonc/). These findings reflect the ongoing efforts to refine treatment strategies and improve outcomes for pediatric patients with brain tumors.