Recent advancements in glioblastoma treatment have focused on innovative therapies, particularly chimeric antigen receptor (CAR) T cell therapies. A study by Choi et al. explored the use of CARv3-TEAM-E T cells, which target both the epidermal growth factor receptor (EGFR) variant III and the wild-type EGFR. This first-in-human trial demonstrated rapid radiographic tumor regression in two out of three participants, although responses were transient, highlighting the need for sustained therapeutic strategies (ref: Choi doi.org/10.1056/NEJMoa2314390/). Similarly, Brown et al. reported on a phase 1 trial of locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma, confirming the feasibility and safety of this approach without dose-limiting toxicities, thus paving the way for further investigations into optimal dosing strategies (ref: Brown doi.org/10.1038/s41591-024-02875-1/). Bagley et al. also contributed to this theme by presenting interim results from a phase 1 trial of intrathecally delivered bivalent CAR T cells targeting EGFR and IL13Rα2, emphasizing the importance of safety and maximum tolerated dose determination in this patient population (ref: Bagley doi.org/10.1038/s41591-024-02893-z/). Collectively, these studies underscore the potential of CAR T cell therapies in glioblastoma treatment, while also indicating the necessity for ongoing research to enhance the durability of responses and expand treatment options.

The tumor microenvironment plays a critical role in shaping the efficacy of immunotherapy, as highlighted by recent studies. Tan et al. developed a machine learning classifier, predicTCR, which identifies tumor-reactive T cell receptors (TCRs) from single-cell RNA sequencing data, thereby facilitating personalized T cell therapies (ref: Tan doi.org/10.1038/s41587-024-02161-y/). This innovative approach addresses the challenges of identifying effective TCRs for transgenic therapies, potentially improving patient outcomes. In a clinical context, Nikitas et al. conducted a phase 2 trial evaluating the addition of dual androgen receptor pathway inhibitors and metastasis-directed stereotactic body radiotherapy to intermittent androgen deprivation therapy in metastatic prostate cancer, demonstrating improved recurrence rates (ref: Nikitas doi.org/10.1016/j.eururo.2024.01.021/). Furthermore, Palma et al. assessed the safety and efficacy of stereotactic radiation therapy in patients with early non-small cell lung cancer and interstitial lung disease, providing insights into treatment tolerability in high-risk populations (ref: Palma doi.org/10.1001/jamaoncol.2023.7269/). Together, these studies illustrate the dynamic interplay between tumor microenvironments and therapeutic strategies, emphasizing the need for tailored approaches in cancer treatment.

Neurosurgical techniques continue to evolve, with recent studies focusing on optimizing patient outcomes through innovative methodologies. Brum et al. investigated blood-based biomarkers to enhance tau-PET scan referrals in memory clinics, aiming to improve prognostic evaluations in Alzheimer's disease (ref: Brum doi.org/10.1038/s41467-024-46603-2/). This approach could streamline diagnostic processes and facilitate timely interventions. Gupta et al. conducted a meta-analysis on the benefits of stereotactic radiosurgical anterior capsulotomy for treatment-resistant obsessive-compulsive disorder, revealing its potential as a minimally invasive therapeutic option (ref: Gupta doi.org/10.3171/2024.1.JNS231537/). Additionally, Iktimal et al. developed an optimized multilayer perceptron for sensorimotor functional mapping using intracranial electroencephalogram data, demonstrating high accuracy in identifying critical brain regions in epilepsy patients (ref: Iktimal doi.org/10.1002/ana.26915/). These advancements underscore the importance of integrating novel technologies and techniques in neurosurgery to enhance diagnostic accuracy and therapeutic efficacy.

Genetic and molecular research has provided significant insights into various neurological disorders, particularly through comprehensive genomic analyses. Fehlings et al. performed whole-genome sequencing in children with cerebral palsy, identifying pathogenic variants in 11.3% of cases and variants of uncertain significance in 17.7%, thus contributing to the understanding of the genetic architecture of this condition (ref: Fehlings doi.org/10.1038/s41588-024-01686-x/). Sidpra et al. expanded on this by analyzing inherited glycosylphosphatidylinositol deficiency disorders, revealing a diverse phenotypic spectrum and the involvement of multiple GPI-AP genes in neurogenetic diseases (ref: Sidpra doi.org/10.1093/brain/). Furthermore, Chelban et al. identified biallelic NAA60 variants linked to primary familial brain calcifications, shedding light on the molecular mechanisms underlying this disorder (ref: Chelban doi.org/10.1038/s41467-024-46354-0/). Collectively, these studies highlight the critical role of genetic research in elucidating the complexities of neurological disorders and the potential for developing targeted therapies.

Research into neurodegenerative diseases has increasingly focused on identifying biomarkers that can aid in early diagnosis and treatment. Rutledge et al. conducted a comprehensive proteomic analysis, discovering that DDC levels in cerebrospinal fluid correlate with clinical symptom severity in Parkinson's disease, thus offering a potential diagnostic biomarker (ref: Rutledge doi.org/10.1007/s00401-024-02706-0/). Yamada et al. explored the role of the transposase-derived PGBD5 in promoting genomic rearrangements in childhood tumors, providing insights into the mutagenic processes underlying medulloblastoma (ref: Yamada doi.org/10.1126/sciadv.adn4649/). Additionally, Zirem et al. assessed the glioblastoma tumor microenvironment using SpiderMass, emphasizing the importance of real-time assessments for improving patient management (ref: Zirem doi.org/10.1016/j.xcrm.2024.101482/). These findings underscore the potential of biomarkers in enhancing our understanding of neurodegenerative diseases and guiding therapeutic strategies.

Advancements in neuroimaging and brain mapping techniques are revolutionizing our understanding of brain function and pathology. 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/). Eide et al. utilized cerebrospinal fluid tracers in MRI to investigate the functional anatomy of the human perivascular subarachnoid space, enhancing our understanding of cerebrospinal fluid dynamics (ref: Eide doi.org/10.1038/s41467-024-46329-1/). Furthermore, Han et al. introduced Janus microparticles for targeted neural stimulation via low-intensity focused ultrasound, representing a novel approach to non-invasive brain stimulation (ref: Han doi.org/10.1038/s41467-024-46245-4/). These innovative techniques highlight the potential for improved diagnostic and therapeutic applications in neurology.

Neuroinflammation and its role in stroke pathology have garnered significant research attention, with recent studies exploring therapeutic interventions. Boisserand et al. demonstrated that VEGF-C prophylaxis enhances lymphatic drainage and modulates neuroinflammation in a stroke model, suggesting a potential therapeutic avenue for stroke management (ref: Boisserand doi.org/10.1084/jem.20221983/). Arkelius et al. investigated the effects of LOX-1 and MMP-9 inhibition on outcomes after acute ischemic stroke, finding that these interventions improved neurological function and reduced infarct size (ref: Arkelius doi.org/10.1161/CIRCRESAHA.123.323371/). Mu et al. introduced a neutrophil targeting platform to reduce neutrophil extracellular traps in traumatic brain injury and stroke, highlighting a novel strategy for mitigating neuroinflammation (ref: Mu doi.org/10.1002/advs.202308719/). Collectively, these studies underscore the importance of targeting neuroinflammation in stroke and brain injury therapies.

Clinical trials in neurosurgery are increasingly focusing on personalized approaches to patient management. Tan et al. highlighted the use of a machine learning classifier to predict tumor-reactive T cell receptors for personalized T cell therapy, which could significantly enhance treatment efficacy (ref: Tan doi.org/10.1038/s41587-024-02161-y/). Brum et al. emphasized the role of blood-based biomarkers in guiding tau-PET referrals, aiming to optimize prognostic evaluations in Alzheimer's disease (ref: Brum doi.org/10.1038/s41467-024-46603-2/). Gupta et al. conducted a meta-analysis on the effectiveness of stereotactic radiosurgical anterior capsulotomy for obsessive-compulsive disorder, providing insights into its risk-benefit profile (ref: Gupta doi.org/10.3171/2024.1.JNS231537/). These studies reflect a growing trend towards integrating advanced technologies and personalized strategies in clinical trials to improve patient outcomes in neurosurgery.