Recent research has focused on the intricate molecular mechanisms underlying gliomas, emphasizing the role of inflammation and genetic alterations. Gandhi et al. highlight the significance of systemic inflammation in glioma progression, suggesting that inflammatory responses initiated by traumatic events in the brain can lead to chronic inflammation, which is detrimental to patient outcomes (ref: Gandhi doi.org/10.5306/wjco.v12.i10.947/). In a complementary study, Bakr et al. reveal that the inhibitor of DNA-binding 3 (ID3) plays a dual role in promoting homologous recombination, a critical DNA repair process, and its loss is associated with increased sensitivity to PARP inhibitors, indicating potential therapeutic targets for glioma treatment (ref: Bakr doi.org/10.1093/nar/). Liu et al. introduce BrainBase, a comprehensive knowledgebase that consolidates data on brain diseases, including gliomas, linking 7175 disease-gene associations and offering insights into potential biomarkers for diagnosis and treatment (ref: Liu doi.org/10.1093/nar/). Furthermore, Ang et al. investigate the trafficking of nanoparticles in glioblastomas, demonstrating that ligand-modified nanoparticles can effectively cross the blood-brain barrier and enhance the efficacy of metronomic chemotherapy, thus presenting a promising avenue for targeted glioma therapies (ref: Ang doi.org/10.1002/adma.202106194/). The prevalence of BRAFV600 mutations in gliomas and the efficacy of BRAF inhibitors were systematically reviewed by Andrews et al., revealing significant response rates in both low-grade and high-grade gliomas, which underscores the importance of genetic profiling in treatment strategies (ref: Andrews doi.org/10.1093/neuonc/). Lastly, Yu et al. explore the molecular diversity of interneurons in the human fetal brain, providing insights into the developmental aspects that may influence glioma pathogenesis (ref: Yu doi.org/10.1038/s41593-021-00940-3/).

The exploration of immunotherapy in brain tumors has gained momentum, particularly in understanding immune-related adverse events (irAEs) and treatment efficacy. Schneider et al. provide updated guidelines for managing irAEs in patients undergoing immune checkpoint inhibitor therapy, emphasizing the need for multidisciplinary approaches to enhance patient outcomes (ref: Schneider doi.org/10.1200/JCO.21.01440/). Santomasso et al. extend this discussion to chimeric antigen receptor (CAR) T-cell therapy, outlining strategies to mitigate irAEs and improve the safety profile of this promising treatment modality (ref: Santomasso doi.org/10.1200/JCO.21.01992/). Tawbi et al. present long-term outcomes from the CheckMate 204 study, demonstrating that combination therapy with nivolumab and ipilimumab yields significant intracranial clinical benefits in melanoma patients with brain metastases, with a 36-month overall survival rate of 71.9% (ref: Tawbi doi.org/10.1016/S1470-2045(21)00545-3/). In contrast, Izquierdo et al. highlight the challenges faced in treating diffuse intrinsic pontine gliomas (DIPGs) with MEK inhibitors, noting the emergence of resistance mechanisms that complicate treatment efficacy (ref: Izquierdo doi.org/10.1158/2159-8290.CD-20-0930/). Rivero-Hinojosa et al. advance the field by developing a proteogenomic approach to identify neoantigens in pediatric brain tumors, facilitating personalized T cell immunotherapy (ref: Rivero-Hinojosa doi.org/10.1038/s41467-021-26936-y/). Wang et al. further elucidate the immunosuppressive mechanisms in glioblastoma, revealing that CD73-positive extracellular vesicles inhibit T-cell expansion, thereby contributing to the tumor's immune evasion strategies (ref: Wang doi.org/10.1038/s41419-021-04359-3/).

Innovative therapeutic strategies and drug development efforts are crucial in addressing the challenges posed by brain tumors. Chen et al. conducted a randomized clinical trial to evaluate the safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia, demonstrating its potential to induce γ-globin expression, although its direct implications for glioma treatment remain to be fully explored (ref: Chen doi.org/10.1038/s41392-021-00811-0/). Wang et al. investigated mefatinib as a first-line treatment for advanced EGFR-mutant non-small-cell lung cancer, providing insights into its efficacy and safety, which may inform similar approaches in glioma therapy (ref: Wang doi.org/10.1038/s41392-021-00773-3/). The development of automated brain tumor segmentation techniques using deep convolutional neural networks was presented by Wang et al., highlighting the importance of advanced imaging analysis in improving diagnostic accuracy and treatment planning (ref: Wang doi.org/10.1016/j.media.2021.102259/). Lassman et al. assessed the efficacy of selinexor in recurrent glioblastoma, revealing promising results that warrant further investigation in combination therapies (ref: Lassman doi.org/10.1158/1078-0432.CCR-21-2225/). Matteoni et al. explored the repurposing of chlorpromazine for glioblastoma treatment, demonstrating its ability to induce cytotoxic autophagy through endoplasmic reticulum stress, which may offer a novel therapeutic avenue (ref: Matteoni doi.org/10.1186/s13046-021-02144-w/). Additionally, Dar et al. elucidated the role of GAPDH in enhancing the therapeutic potential of extracellular vesicles for siRNA delivery, showcasing the promise of nanotechnology in drug delivery systems (ref: Dar doi.org/10.1038/s41467-021-27056-3/).

Clinical outcomes and treatment efficacy in brain tumors are critical areas of research that inform therapeutic strategies. Armstrong et al. discuss the challenges faced in conducting clinical trials for rare CNS tumors, emphasizing the need for collaborative networks to enhance patient accrual and ensure adequate power for evaluating new treatments (ref: Armstrong doi.org/10.1093/neuonc/). The consensus review by Frappaz et al. on the management of intracranial germ cell tumors highlights the importance of tailored treatment approaches to minimize long-term sequelae, particularly in adolescents and young adults (ref: Frappaz doi.org/10.1093/neuonc/). Nassiri et al. present core clinical data elements for meningiomas, advocating for standardized data collection to facilitate comparative analyses and improve clinical outcomes (ref: Nassiri doi.org/10.1093/neuonc/). Yu et al. contribute to the understanding of interneuron diversity in the human fetal brain, which may have implications for neurodevelopmental aspects of brain tumors (ref: Yu doi.org/10.1038/s41593-021-00940-3/). Huo et al. investigate the role of TRPC5 in neuroinflammation and memory impairment, suggesting potential therapeutic targets for cognitive deficits associated with brain tumors (ref: Huo doi.org/10.1186/s12974-021-02321-w/). The upregulation of TRPC5 in hippocampal excitatory synapses is shown to improve memory performance in a neuroinflammatory model, indicating the interplay between neuroinflammation and cognitive function (ref: Huo doi.org/10.1186/s12974-021-02321-w/).

Neuroinflammation and the tumor microenvironment play pivotal roles in the progression and treatment of brain tumors. Babikir et al. investigate the regulatory role of ATRX in glial identity and the tumor microenvironment in IDH-mutant gliomas, revealing significant transcription factor expression differences that may influence therapeutic responses (ref: Babikir doi.org/10.1186/s13059-021-02535-4/). Lee et al. explore the effects of neoadjuvant PD-1 blockade in recurrent glioblastoma, noting that while T cell activation occurs, the presence of immunosuppressive tumor-associated macrophages limits the overall efficacy of this approach (ref: Lee doi.org/10.1038/s41467-021-26940-2/). The dual role of allele-specific DNA hypermethylation within the TERT promoter in cancer is examined by Lee et al., providing insights into the epigenetic regulation of tumor biology (ref: Lee doi.org/10.1172/JCI146915/). Chen et al. discuss the temporal inhibition of chromatin looping during neuronal remodeling, which may have implications for understanding neuroinflammatory processes in brain tumors (ref: Chen doi.org/10.1038/s41467-021-26628-7/). Zhang et al. highlight the prognostic significance of telomerase-positive circulating tumor cells in glioma, linking their presence to a neutrophil-mediated inflammatory immune environment (ref: Zhang doi.org/10.1186/s12916-021-02138-7/). Jiang et al. investigate the mechanisms of tumor innervation triggered by endoplasmic reticulum stress, suggesting potential therapeutic targets to disrupt tumor progression (ref: Jiang doi.org/10.1038/s41388-021-02108-6/).

Nanotechnology and drug delivery systems are revolutionizing the treatment landscape for brain tumors, offering innovative approaches to enhance therapeutic efficacy. Jiang et al. present cation-free siRNA micelles as a potent drug delivery platform, demonstrating their ability to synergistically enhance the effects of temozolomide in glioblastoma therapy (ref: Jiang doi.org/10.1002/adma.202104779/). Ang et al. further explore nanoparticle trafficking in glioblastomas, revealing that ligand-modified nanoparticles can effectively traverse the blood-brain barrier and enhance the antitumor effects of metronomic chemotherapy (ref: Ang doi.org/10.1002/adma.202106194/). Dar et al. investigate the role of GAPDH in extracellular vesicle biogenesis, highlighting its potential to enhance the therapeutic delivery of siRNA to the brain (ref: Dar doi.org/10.1038/s41467-021-27056-3/). Wang et al. develop a microfluidics-based approach to generate extracellular vesicles with enhanced therapeutic microRNA loading, addressing challenges in clinical translation due to size heterogeneity and loading efficiency (ref: Wang doi.org/10.1021/acsnano.1c07587/). Lassman et al. assess the safety and efficacy of selinexor in recurrent glioblastoma, emphasizing the need for ongoing trials to evaluate its potential in combination therapies (ref: Lassman doi.org/10.1158/1078-0432.CCR-21-2225/). Matteoni et al. explore the cytotoxic effects of chlorpromazine in glioblastoma cells, suggesting its potential as a repurposed therapeutic agent (ref: Matteoni doi.org/10.1186/s13046-021-02144-w/).

The genetic and epigenetic landscape of brain tumors is crucial for understanding their biology and developing targeted therapies. Bakr et al. investigate the role of ID3 in promoting homologous recombination, revealing its potential as a therapeutic target in gliomas with DNA repair defects (ref: Bakr doi.org/10.1093/nar/). Liu et al. introduce BrainBase, a curated knowledgebase that compiles extensive data on brain diseases and associated genetic alterations, providing a valuable resource for researchers (ref: Liu doi.org/10.1093/nar/). Lee et al. examine the dual role of allele-specific DNA hypermethylation within the TERT promoter, highlighting its implications for telomerase activation in cancer (ref: Lee doi.org/10.1172/JCI146915/). Andrews et al. conduct a systematic review on the prevalence of BRAFV600 mutations in gliomas, demonstrating significant treatment responses to BRAF inhibitors, which underscores the importance of genetic profiling in clinical decision-making (ref: Andrews doi.org/10.1093/neuonc/). Wang et al. explore the immunosuppressive role of CD73-positive extracellular vesicles in glioblastoma, linking their presence to the tumor's ability to evade immune detection (ref: Wang doi.org/10.1038/s41419-021-04359-3/). Rivero-Hinojosa et al. develop a proteogenomic approach to identify neoantigens in pediatric brain tumors, facilitating personalized immunotherapy strategies (ref: Rivero-Hinojosa doi.org/10.1038/s41467-021-26936-y/).