Recent advancements in innovative therapies for glioblastoma have focused on the application of engineered T cell therapies and metabolic interventions. A notable study by Choi et al. introduced CARv3-TEAM-E T cells, which target both the EGFR variant III and wild-type EGFR in recurrent glioblastoma patients. This first-in-human trial demonstrated rapid radiographic tumor regression in two out of three participants following a single intraventricular infusion, although responses were transient (ref: Choi doi.org/10.1056/NEJMoa2314390/). In a similar vein, Bagley et al. reported interim results from a phase 1 trial involving intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2, emphasizing the need for safety and maximum tolerated dose assessments in recurrent glioblastoma (ref: Bagley doi.org/10.1038/s41591-024-02893-z/). Furthermore, Tan et al. explored personalized T cell therapy by predicting tumor-reactive T cell receptors from single-cell RNA sequencing data, which could enhance the efficacy of individualized treatments (ref: Tan doi.org/10.1038/s41587-024-02161-y/). Wu et al. identified the role of threonine in fueling glioblastoma through YRDC-mediated translational reprogramming, suggesting metabolic pathways as potential therapeutic targets (ref: Wu doi.org/10.1038/s43018-024-00748-7/). Lastly, de la Nava et al. demonstrated that the oncolytic adenovirus Delta-24-RGD combined with ONC201 induces significant antitumor responses in pediatric high-grade glioma models, highlighting the potential of viral therapies in this context (ref: de la Nava doi.org/10.1093/neuonc/). Collectively, these studies underscore a multifaceted approach to glioblastoma treatment, integrating immunotherapy and metabolic modulation.

The tumor microenvironment plays a critical role in shaping immune responses in glioblastoma, as evidenced by several recent studies. Xu et al. revealed that multiple cancer cell types can hijack neural signals by releasing LIF and Gal3, which may influence cancer prognosis through interactions with the nervous system (ref: Xu doi.org/10.1038/s41422-024-00946-z/). In a longitudinal analysis, de Blank et al. highlighted the evolution of pediatric glioma therapies, noting a significant reduction in radiation exposure over time, which correlates with improved long-term outcomes in adult survivors (ref: de Blank doi.org/10.1038/s43018-024-00733-0/). Chen et al. investigated the synergistic effects of bacteria and PD-1 blockade in glioma, demonstrating that Porphyromonas gingivalis can enhance the immune response, transforming gliomas from 'cold' to 'hot' tumors (ref: Chen doi.org/10.1002/advs.202308124/). Wang et al. further elucidated the impact of chronic stress on glioma progression, showing that stress hormones inhibit CCL3 secretion, thereby exacerbating the immunosuppressive microenvironment (ref: Wang doi.org/10.1158/2326-6066.CIR-23-0378/). Additionally, Li et al. introduced a novel thermogel that dual-regulates metabolism and immunity, enhancing glioblastoma immunotherapy by inhibiting lactate excretion and PD-1/PD-L1 interactions (ref: Li doi.org/10.1002/advs.202310163/). These findings collectively emphasize the intricate interplay between the tumor microenvironment and immune responses, suggesting that targeting these interactions may enhance therapeutic efficacy.

Genomic and molecular research in neuro-oncology has provided significant insights into the mechanisms underlying brain tumors and potential therapeutic targets. Rastogi et al. developed a deep learning-based method for reconstructing undersampled MRI data, significantly reducing scan times while maintaining image quality, which is crucial for oncological imaging (ref: Rastogi doi.org/10.1016/S1470-2045(23)00641-1/). Zhang et al. investigated the role of SLC25A15 in hepatocellular carcinoma, revealing its impact on glutamine metabolism and tumor progression, thereby highlighting metabolic pathways as potential therapeutic targets (ref: Zhang doi.org/10.1016/j.jhep.2023.10.024/). Hwang et al. identified a benzarone derivative that inhibits EYA proteins, suppressing tumor growth in Sonic Hedgehog medulloblastoma models, indicating the importance of targeting specific molecular pathways in cancer treatment (ref: Hwang doi.org/10.1158/0008-5472.CAN-22-3784/). Peng et al. reported on a biomimetic nanocomplex that enhances glioma immunotherapy by modulating T cell and NK cell activity, showcasing the potential of nanomedicine in cancer treatment (ref: Peng doi.org/10.1021/acsnano.3c13088/). Lastly, Cornel et al. explored the potential of MR1-restricted T cells in targeting pediatric cancers, proposing a novel immunotherapy approach that could overcome HLA-restriction challenges (ref: Cornel doi.org/10.1136/jitc-2023-007538/). These studies collectively underscore the importance of genomic and molecular insights in developing innovative therapeutic strategies for neuro-oncology.

Clinical outcomes and treatment strategies for glioblastoma have been the focus of several recent studies aimed at improving patient management. Caccese et al. conducted a large multicenter observational study evaluating the efficacy and safety of regorafenib in recurrent glioblastoma, confirming the findings of the REGOMA trial in a real-world setting, with similar overall survival and improved tolerability (ref: Caccese doi.org/10.1016/j.esmoop.2024.102943/). Roth et al. reported on a randomized phase 3 trial of marizomib for newly diagnosed glioblastoma, finding no significant difference in overall survival or progression-free survival compared to standard therapy, particularly in patients with unmethylated MGMT promoter tumors (ref: Roth doi.org/10.1093/neuonc/). Álvarez-Vázquez et al. highlighted the role of EGFR alterations in predicting responses to TAT-Cx43266-283 in preclinical glioblastoma models, suggesting that targeting these alterations may enhance treatment efficacy (ref: Álvarez-Vázquez doi.org/10.1093/neuonc/). These studies illustrate the ongoing efforts to refine treatment strategies and improve clinical outcomes for glioblastoma patients, emphasizing the need for personalized approaches based on molecular characteristics.

Neuroinflammation and neurodegeneration are critical areas of research, particularly in understanding the long-term effects of infections and the mechanisms underlying neurodegenerative diseases. Partiot et al. demonstrated that SARS-CoV-2 infection disrupts synaptic homeostasis, potentially leading to neurological complications associated with COVID-19 (ref: Partiot doi.org/10.1038/s41564-024-01657-2/). Cubillos et al. investigated the role of EPIREGULIN in promoting basal progenitor cell proliferation in the developing neocortex, suggesting that this growth factor may influence neurodevelopmental processes (ref: Cubillos doi.org/10.1038/s44318-024-00068-7/). Additionally, Fu et al. explored the role of the alpha5 nicotine acetylcholine receptor subunit in promoting intrahepatic cholangiocarcinoma metastasis, linking neurotransmitter signaling to cancer progression (ref: Fu doi.org/10.1038/s41392-024-01761-z/). Fan et al. proposed targeting pro-inflammatory T cells as a novel therapeutic strategy to address atherosclerosis, highlighting the intersection of inflammation and neurodegeneration in chronic diseases (ref: Fan doi.org/10.1038/s41422-024-00945-0/). These findings underscore the complex interplay between neuroinflammation and neurodegeneration, suggesting that targeting inflammatory pathways may offer new therapeutic avenues.

Recent advancements in biomarkers and diagnostic innovations have the potential to significantly enhance cancer detection and treatment monitoring. Marcuccio et al. introduced a single-cell nanobiopsy platform that allows for longitudinal transcriptomic profiling of glioblastoma cells, providing insights into cellular dynamics without cell lysis (ref: Marcuccio doi.org/10.1126/sciadv.adl0515/). Zhang et al. examined the role of HDAC3 in regulating microglial proliferation after ischemic stroke, revealing its potential as a therapeutic target for neuroinflammatory conditions (ref: Zhang doi.org/10.1126/sciadv.ade6900/). Senapati et al. developed multifunctional liposomes targeting amyloid-β oligomers for early diagnosis and therapy of Alzheimer's disease, emphasizing the importance of early intervention in neurodegenerative diseases (ref: Senapati doi.org/10.1002/smll.202311670/). Caccese et al. also contributed to this theme with their study on regorafenib in glioblastoma, reinforcing the significance of real-world evidence in validating clinical trial findings (ref: Caccese doi.org/10.1016/j.esmoop.2024.102943/). Collectively, these studies highlight the critical role of biomarkers and innovative diagnostic approaches in improving cancer management and patient outcomes.

Metabolic pathways in cancer have emerged as crucial targets for therapeutic intervention, with recent studies shedding light on their roles in tumor progression and treatment resistance. Zhang et al. investigated the impact of SLC25A15 deficiency on hepatocellular carcinoma, revealing its role in reprogramming glutamine metabolism and promoting tumor growth (ref: Zhang doi.org/10.1016/j.jhep.2023.10.024/). Wang et al. highlighted how chronic stress exacerbates glioma progression by reducing CCL3 secretion, which is essential for recruiting M1-type tumor-associated macrophages (TAMs), thereby linking stress responses to metabolic dysregulation in tumors (ref: Wang doi.org/10.1158/2326-6066.CIR-23-0378/). Li et al. presented a dual-regulation thermogel that inhibits lactate excretion and enhances immunotherapy efficacy in glioblastoma, showcasing the interplay between metabolism and immune responses (ref: Li doi.org/10.1002/advs.202310163/). These findings collectively underscore the importance of understanding metabolic pathways in cancer, as they offer new avenues for therapeutic strategies aimed at disrupting tumor metabolism and enhancing treatment efficacy.