The tumor microenvironment plays a crucial role in shaping the immune response in brain tumors, particularly gliomas and brain metastases. Maas et al. conducted an in-depth analysis of neutrophil phenotypes and functions within glioma and brain metastasis tissues, revealing that the local microenvironment significantly drives neutrophil activation and function (ref: Maas doi.org/10.1016/j.cell.2023.08.043/). This study highlights the complexity of immune cell interactions within brain tumors, suggesting that neutrophils may have context-dependent roles that vary between tumor types. Additionally, Sanchez-Aguilera et al. utilized machine learning to identify distinct subtypes of brain metastases based on their effects on neural circuits, demonstrating that these tumors can disrupt neuronal function beyond mere mass effects (ref: Sanchez-Aguilera doi.org/10.1016/j.ccell.2023.07.010/). This multidimensional modeling approach underscores the heterogeneous impact of brain metastases on cognitive function and neural circuit dynamics. Furthermore, Chen et al. explored a paracrine circuit involving IL-1β and IL-1R1 between myeloid and tumor cells, which drives glioblastoma progression, indicating that inflammatory signaling pathways are critical in tumor growth and immune evasion (ref: Chen doi.org/10.1172/JCI163802/). Collectively, these studies illustrate the intricate interplay between tumor cells and the immune microenvironment, emphasizing the need for targeted therapies that consider these interactions.

Recent advancements in targeted therapies for gliomas have shown promising results, particularly in pediatric populations. Bouffet et al. reported that the combination of dabrafenib and trametinib resulted in a 47% overall response rate in pediatric glioma patients, significantly outperforming traditional chemotherapy (ref: Bouffet doi.org/10.1056/NEJMoa2303815/). This study highlights the potential of targeted therapies to improve clinical outcomes in this vulnerable population. Additionally, Dong et al. introduced a designer peptide targeting the EAG2-Kv2.2 potassium channel, which plays a role in glioblastoma cell interactions with neurons, suggesting a novel therapeutic avenue that could disrupt tumor-brain communication (ref: Dong doi.org/10.1038/s43018-023-00626-8/). Meanwhile, Miyazaki et al. presented vepafestinib, a RET-selective inhibitor with high CNS penetration, which could address the limitations of existing therapies in treating brain metastases (ref: Miyazaki doi.org/10.1038/s43018-023-00630-y/). These findings collectively indicate a shift towards more personalized and effective treatment strategies for gliomas, with a focus on molecular targets and the tumor microenvironment.

Genetic and epigenetic factors significantly influence the behavior and treatment response of brain tumors. Wang et al. demonstrated that genetic intratumor heterogeneity remodels the immune microenvironment in lung cancer brain metastases, leading to immune evasion (ref: Wang doi.org/10.1016/j.jtho.2023.09.276/). This study emphasizes the importance of understanding genetic diversity within tumors to develop effective immunotherapies. Similarly, Pang et al. identified the Kunitz-type protease inhibitor TFPI2 as a key player in promoting glioblastoma stem cell self-renewal and immunosuppression, linking genetic alterations to tumor aggressiveness (ref: Pang doi.org/10.1038/s41590-023-01605-y/). Furthermore, Branzoli et al. utilized in vivo MR spectroscopy to differentiate between IDH-mutant gliomas based on neurochemical profiles, highlighting the potential for non-invasive diagnostic tools to guide treatment decisions (ref: Branzoli doi.org/10.1148/radiol.223255/). These studies underscore the critical role of genetic and epigenetic factors in shaping tumor biology and therapeutic responses, paving the way for more tailored approaches in neuro-oncology.

Imaging and biomarkers are vital for improving diagnosis and treatment outcomes in neuro-oncology. Tobochnik et al. focused on identifying genetic profiles associated with glioma hyperexcitability, revealing that specific somatic mutations correlate with clinical symptoms such as seizures (ref: Tobochnik doi.org/10.1093/neuonc/). This work highlights the potential of genetic profiling to inform clinical management and predict patient outcomes. Additionally, Lauer et al. developed semi-automated 3D tumor volume measurements via MRI, demonstrating that a reduction of 97% in tumor volume serves as a strong predictor of survival in CNS lymphoma patients (ref: Lauer doi.org/10.1093/neuonc/). These advancements in imaging techniques not only enhance the accuracy of tumor assessments but also provide critical information for treatment planning. Moreover, the integration of biomarkers into clinical practice is essential for personalizing therapy and monitoring disease progression, as evidenced by ongoing research in the field.

Clinical trials continue to play a pivotal role in advancing treatment options for brain tumors. The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) showcased a phase II platform trial that utilized adaptive randomization to evaluate multiple experimental therapies against a common control, demonstrating feasibility and promising results (ref: Rahman doi.org/10.1200/JCO.23.00493/). This innovative approach allows for more efficient identification of effective treatments. Additionally, Umemura et al. conducted a phase 1 trial assessing the safety and efficacy of combined cytotoxic and immune-stimulatory gene therapy for high-grade gliomas, which showed potential for further investigation in subsequent trials (ref: Umemura doi.org/10.1016/S1470-2045(23)00347-9/). Furthermore, Westcott et al. highlighted that mismatch repair deficiency, while associated with high tumor mutational burden, does not guarantee durable responses to immune checkpoint blockade, indicating the complexity of tumor immunogenicity (ref: Westcott doi.org/10.1038/s41588-023-01499-4/). These findings emphasize the need for ongoing clinical research to refine treatment strategies and improve patient outcomes.

The neurocognitive effects of brain tumors and their treatments significantly impact patients' quality of life. Remes et al. investigated the long-term cognitive impairments in childhood brain tumor survivors, finding associations between vascular cognitive dysfunction and lower performance in various cognitive domains (ref: Remes doi.org/10.1093/neuonc/). This study underscores the importance of monitoring cognitive health in survivors and developing interventions to mitigate these effects. Additionally, Branzoli et al. explored neurochemical differences between glioma subtypes, which may inform treatment strategies and cognitive outcomes (ref: Branzoli doi.org/10.1148/radiol.223255/). The integration of cognitive assessments into clinical practice is essential for understanding the full impact of brain tumors and their treatments on patients' lives, guiding supportive care and rehabilitation efforts.

Metastasis to the brain presents significant challenges in treatment and management. Wang et al. highlighted the role of genetic intratumor heterogeneity in lung cancer brain metastases, which remodels the immune microenvironment and facilitates immune evasion (ref: Wang doi.org/10.1016/j.jtho.2023.09.276/). This finding emphasizes the need for targeted therapies that address the unique characteristics of metastatic tumors. Sanchez-Aguilera et al. utilized machine learning to identify brain metastasis subtypes based on their effects on neural circuits, revealing the complex interplay between tumor growth and cognitive function (ref: Sanchez-Aguilera doi.org/10.1016/j.ccell.2023.07.010/). Furthermore, the study by Deshpande et al. on breast cancer metastasis to the brain elucidated the mechanisms underlying neural adaptation and tumor colonization, highlighting the importance of understanding these processes for developing effective treatments (ref: Deshpande doi.org/10.1093/neuonc/). Collectively, these studies underscore the critical need for innovative strategies to combat brain metastases and improve patient outcomes.

Innovations in surgical techniques and technologies are transforming the landscape of neuro-oncology. Price et al. developed a joystick-controlled endoscopic robot aimed at reducing the invasiveness of brain surgeries while maintaining the precision of open surgical techniques (ref: Price doi.org/10.1126/scirobotics.adg6042/). This advancement could significantly enhance surgical outcomes and patient recovery times. Additionally, Petronek et al. explored the use of pharmacologic ascorbate in combination with radiation and temozolomide for glioblastoma treatment, investigating T2* mapping as a non-invasive biomarker to predict treatment response (ref: Petronek doi.org/10.1158/1078-0432.CCR-22-3952/). This approach highlights the potential for integrating imaging technologies with novel therapeutic strategies. Furthermore, Johnson et al. examined the effects of age on glioblastoma outcomes, revealing that older patients may benefit from senolytic therapies to enhance immunotherapy responses (ref: Johnson doi.org/10.1158/1078-0432.CCR-23-0834/). These innovations reflect a growing trend towards personalized and less invasive treatment options in neuro-oncology.