The tumor microenvironment plays a critical role in the progression and treatment response of gliomas. One study investigated the delivery of an oncolytic adenovirus via neural stem cells (NSCs) in patients with malignant glioma, demonstrating that this approach is safe and shows potential efficacy in targeting tumor cells (ref: Fares doi.org/10.1016/S1470-2045(21)00245-X/). Another study highlighted the role of pericytes in enhancing glioblastoma cell resistance to temozolomide through CCL5-CCR5 signaling, indicating that the perivascular niche contributes to chemoresistance (ref: Zhang doi.org/10.1038/s41422-021-00528-3/). Additionally, research on IDH mutant glioma-derived extracellular vesicles revealed their capacity to induce systemic immunosuppression, reducing the presence of effector lymphocytes and macrophages in tumor-bearing mice (ref: Ludwig doi.org/10.1093/neuonc/). These findings emphasize the complex interactions within the tumor microenvironment that can influence treatment outcomes and highlight the need for strategies that can effectively target these interactions to improve patient responses to therapy.

Innovative therapeutic strategies are being explored to improve outcomes in neuro-oncology, particularly for glioblastoma. A phase 1 trial assessed the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by NSCs, showing promise in newly diagnosed high-grade glioma patients (ref: Fares doi.org/10.1016/S1470-2045(21)00245-X/). Another study proposed a patient stratification strategy to enhance the efficacy of dasatinib, a Src inhibitor, in glioblastoma by classifying tumors into distinct genomic subtypes, which may improve therapeutic targeting (ref: Alhalabi doi.org/10.1093/neuonc/). Furthermore, the development of lisavanbulin, a tumor checkpoint controller, demonstrated potential in preclinical models, suggesting that combining it with standard therapies could enhance treatment efficacy (ref: Burgenske doi.org/10.1093/neuonc/). These studies collectively underscore the importance of personalized approaches and novel agents in the treatment of gliomas.

Understanding the genetic and molecular mechanisms underlying gliomas is crucial for developing targeted therapies. Research into the H3-K27M mutation, prevalent in pediatric brain tumors, revealed that it disrupts PRC2 function and enhancer activity, contributing to oncogenic processes (ref: Brien doi.org/10.1038/s41588-021-00897-w/). Additionally, a genomic atlas of protein levels in brain tissues identified significant protein quantitative trait loci, which may inform the development of biomarkers for neurological disorders (ref: Yang doi.org/10.1038/s41593-021-00886-6/). Furthermore, the role of BEX1 in regulating stemness and tumorigenicity in liver cancer was highlighted, suggesting that similar mechanisms may be at play in gliomas (ref: Wang doi.org/10.1016/j.jhep.2021.06.025/). These insights into the molecular landscape of gliomas can guide future therapeutic strategies aimed at specific genetic alterations.

Patient-derived models are essential for studying gliomas and testing new therapies. A study established 21 patient-derived orthotopic xenograft (PDOX) models of pediatric high-grade glioma, which recapitulated the heterogeneity of molecular signatures and drug responses, providing a valuable platform for identifying therapeutic vulnerabilities (ref: He doi.org/10.1038/s41467-021-24168-8/). Additionally, the use of patient-derived xenografts to evaluate the efficacy of lisavanbulin demonstrated its potential as a novel treatment strategy for glioblastoma (ref: Burgenske doi.org/10.1093/neuonc/). These models not only facilitate the understanding of tumor biology but also enable the testing of personalized treatment approaches, thereby enhancing the translational potential of preclinical findings to clinical settings.

Clinical outcomes in neuro-oncology are increasingly influenced by patient stratification strategies. The PERUSE study evaluated the combination of pertuzumab and trastuzumab in HER2-positive breast cancer, demonstrating improved outcomes through a multivariable prognostication approach (ref: Miles doi.org/10.1016/j.annonc.2021.06.024/). In pediatric oncology, a randomized trial showed that therapy intensification with carboplatin improved event-free survival in children with high-risk medulloblastoma, emphasizing the importance of tailored treatment regimens (ref: Leary doi.org/10.1001/jamaoncol.2021.2224/). Furthermore, the stratification of glioblastoma patients based on genomic signatures has the potential to enhance therapeutic efficacy, as seen with dasatinib (ref: Alhalabi doi.org/10.1093/neuonc/). These findings highlight the critical role of personalized medicine in improving clinical outcomes for patients with brain tumors.