The tumor microenvironment (TME) plays a critical role in tumor progression and immune evasion. Recent studies have highlighted the reciprocal interactions between innate immune cells and astrocytes, particularly in the context of brain metastasis. For instance, research by Adler et al. demonstrates that granulocyte-derived lipocalin-2 (LCN2) activates astrocytes, which in turn recruit myeloid cells to the brain, facilitating the metastasis of melanoma and breast cancer (ref: Adler doi.org/10.1038/s43018-023-00519-w/). This finding underscores the importance of understanding how immune cells contribute to the neuroinflammatory processes that promote tumor growth in the brain. Furthermore, Yang et al. explored the potential of toosendanin, a small-molecule compound, to reprogram macrophages within the glioblastoma TME, enhancing antitumor immunity and overcoming resistance to immunotherapy (ref: Yang doi.org/10.1126/scitranslmed.abq3558/). In a different approach, Turco et al. demonstrated that TLR7/8-agonist-loaded nanoparticles can induce a T cell-independent immune response, reshaping the immunosuppressive TME in glioblastoma (ref: Turco doi.org/10.1038/s41467-023-36321-6/). Collectively, these studies illustrate the dynamic interplay between immune cells and the TME, highlighting potential therapeutic strategies to enhance immune responses against tumors.

Targeted therapies have emerged as a cornerstone in the treatment of various cancers, including glioblastoma and medulloblastoma. Recent research has identified critical molecular targets that can be exploited for therapeutic gain. For example, Migliozzi et al. utilized integrative multi-omics approaches to identify PKCδ and DNA-PK as master kinases in glioblastoma subtypes, providing insights into subtype-specific therapeutic strategies (ref: Migliozzi doi.org/10.1038/s43018-022-00510-x/). This study emphasizes the need for precision medicine approaches that consider the molecular heterogeneity of tumors. Additionally, Long et al. reported that GPR162 acts as a novel tumor suppressor by activating the STING-dependent DNA damage pathway, enhancing the efficacy of radiotherapy (ref: Long doi.org/10.1038/s41392-022-01224-3/). These findings are complemented by Kwon et al., who developed a single-cell expression atlas to identify optimal target antigens for CAR T-cell therapy, addressing the challenge of intratumoral heterogeneity (ref: Kwon doi.org/10.1038/s41587-023-01686-y/). Together, these studies highlight the potential of targeted therapies to improve outcomes in patients with aggressive brain tumors.

Clinical trials in neuro-oncology face unique challenges, particularly in terms of enrollment and reporting outcomes. Kim et al. conducted a critical analysis of neuro-oncology clinical trials, revealing that only 42% were completed, with a significant proportion failing to meet enrollment targets (ref: Kim doi.org/10.1093/neuonc/). This highlights the need for improved strategies to enhance trial participation and reporting. In terms of treatment outcomes, De Roeck et al. performed a meta-analysis assessing cognitive outcomes in glioma patients, finding significant cognitive decline post-treatment, which underscores the importance of monitoring cognitive function as a secondary outcome in clinical trials (ref: De Roeck doi.org/10.1093/neuonc/). Furthermore, Salem et al. explored innovative treatment strategies for immune-checkpoint inhibitor-associated myocarditis, demonstrating the potential of combined therapies to mitigate severe adverse effects (ref: Salem doi.org/10.1158/2159-8290.CD-22-1180/). These findings emphasize the critical need for comprehensive approaches in clinical trials to improve patient outcomes in neuro-oncology.

Recent advancements in genomic and epigenomic research have provided significant insights into the molecular underpinnings of brain tumors. Foss-Skiftesvik et al. conducted a multi-ancestry genome-wide association study, identifying a risk locus at 9p21.3 associated with pediatric glioma, thus highlighting the genetic factors contributing to tumor susceptibility (ref: Foss-Skiftesvik doi.org/10.1093/neuonc/). In parallel, Zou et al. uncovered a neurodevelopmental epigenetic program that is hijacked in medulloblastoma, revealing how alterations in signaling pathways can promote tumor metastasis (ref: Zou doi.org/10.1038/s41556-023-01093-0/). Additionally, Luo et al. demonstrated that loss of the phosphatase CTDNEP1 leads to MYC amplification and genomic instability in medulloblastoma, suggesting a critical role for this gene in tumor aggressiveness (ref: Luo doi.org/10.1038/s41467-023-36400-8/). Collectively, these studies underscore the importance of genomic and epigenomic factors in understanding tumor biology and developing targeted therapies.

Tumor heterogeneity poses significant challenges in the treatment of brain tumors, particularly in understanding resistance mechanisms. Kwon et al. addressed this issue by mapping combinatorial target antigens for CAR T-cell therapy, emphasizing the need to identify specific antigens that can effectively distinguish malignant cells from normal tissue (ref: Kwon doi.org/10.1038/s41587-023-01686-y/). This study highlights the complexity of tumor microenvironments and the necessity for tailored therapeutic strategies. Additionally, Peng et al. explored the predictive value of circulating tumor DNA and T cell repertoire in assessing treatment response in non-small cell lung cancer patients with brain metastasis, indicating that these biomarkers could guide therapeutic decisions (ref: Peng doi.org/10.1002/cac2.12410/). Furthermore, Lee et al. investigated the role of vascular remodeling in glioblastoma invasion, providing insights into how tumor cells exploit the vasculature for metastasis (ref: Lee doi.org/10.1038/s12276-023-00939-9/). These findings collectively emphasize the need for innovative approaches to overcome tumor heterogeneity and resistance in brain tumors.

Innovative therapeutic strategies are crucial for improving outcomes in patients with brain tumors. Charbonneau et al. developed a rapid patient-derived xenograft model using chicken embryo chorioallantoic membrane (CAM) to predict chemotherapeutic drug sensitivity in high-grade gliomas, providing a promising platform for personalized medicine (ref: Charbonneau doi.org/10.1093/neuonc/). This model addresses the limitations of traditional PDX models, enabling quicker assessments of therapeutic efficacy. Additionally, the study by Adler et al. on the interactions between innate immune cells and astrocytes reveals potential therapeutic targets for enhancing immune responses against brain metastasis (ref: Adler doi.org/10.1038/s43018-023-00519-w/). Moreover, the use of an agonistic anti-Tie2 antibody by Lee et al. demonstrated the ability to suppress tumor vascular transitions, highlighting the importance of targeting the tumor vasculature in glioblastoma treatment (ref: Lee doi.org/10.1038/s12276-023-00939-9/). These innovative approaches underscore the potential for developing effective therapies that can be tailored to individual patient needs.

Neurodevelopmental and genetic factors play a pivotal role in the progression of brain tumors. Zou et al. identified a neurodevelopmental epigenetic program that is hijacked in medulloblastoma, linking abnormal neurodevelopment to tumor aggressiveness (ref: Zou doi.org/10.1038/s41556-023-01093-0/). This study suggests that understanding the developmental pathways involved in tumorigenesis could provide new therapeutic targets. Additionally, Migliozzi et al. highlighted the significance of PKCδ and DNA-PK as master kinases in glioblastoma subtypes, emphasizing the need for targeted therapies that consider the genetic landscape of tumors (ref: Migliozzi doi.org/10.1038/s43018-022-00510-x/). Furthermore, Alemany et al. discussed the impact of health system crises on glioblastoma management, revealing how external factors can influence treatment outcomes (ref: Alemany doi.org/10.1093/neuonc/). These findings collectively underscore the intricate interplay between genetic predispositions and external influences in tumor progression.

Patient-derived models are increasingly recognized as essential tools for advancing personalized medicine in oncology. Charbonneau et al. developed a rapid patient-derived xenograft model using the chicken embryo chorioallantoic membrane (CAM) system, which allows for quick evaluation of drug sensitivity in high-grade gliomas (ref: Charbonneau doi.org/10.1093/neuonc/). This innovative approach addresses the limitations of traditional xenograft models, facilitating timely therapeutic decisions. Additionally, Kwon et al. constructed a single-cell expression atlas to identify target antigens for CAR T-cell therapy, which is crucial for tailoring treatments to individual tumor profiles (ref: Kwon doi.org/10.1038/s41587-023-01686-y/). Furthermore, Peng et al. explored the predictive capabilities of circulating tumor DNA and T cell repertoire in assessing treatment responses, highlighting the potential for these biomarkers to inform personalized therapeutic strategies (ref: Peng doi.org/10.1002/cac2.12410/). Collectively, these studies emphasize the importance of patient-derived models in developing personalized treatment approaches that can improve outcomes for patients with brain tumors.