The tumor microenvironment (TME) plays a critical role in glioblastoma progression and treatment response. Zhong et al. investigated the dual role of TREM2 in glioblastoma-associated myeloid cells, revealing that TREM2 promotes inflammation at the tumor-neural interface while suppressing it within the tumor core, influenced by local microenvironmental factors (ref: Villa doi.org/10.1016/j.ccell.2024.05.018/). This highlights the complexity of immune interactions within the TME and suggests potential avenues for neuro-oncological immunotherapy. Noh et al. focused on reprogramming the TME by targeting IGF2 to enhance the efficacy of oncolytic herpes simplex-1 virus (oHSV) therapy, which is currently limited by TME resistance (ref: Noh doi.org/10.1093/neuonc/). Their RNA sequencing approach identified molecular targets that could be pivotal in overcoming this resistance. Liu et al. further explored immune-related interaction networks in glioblastoma, providing insights into the biological and clinical significance of these networks, which could inform tailored management strategies (ref: Liu doi.org/10.1002/imt2.127/). Najem et al. demonstrated that the STING agonist 8803 can reprogram the immune microenvironment, significantly increasing survival in preclinical models, including those resistant to immune checkpoint blockade (ref: Najem doi.org/10.1172/JCI175033/). Arrieta et al. reported that ultrasound-mediated delivery of doxorubicin enhances immune modulation and improves responses to PD-1 blockade, indicating a synergistic effect of combining chemotherapeutic agents with immunotherapy (ref: Arrieta doi.org/10.1038/s41467-024-48326-w/). Finally, Skadborg et al. showed that nivolumab effectively reaches brain lesions in glioblastoma patients, inducing T-cell activity and upregulating checkpoint pathways, further emphasizing the importance of immune engagement in treatment strategies (ref: Skadborg doi.org/10.1158/2326-6066.CIR-23-0959/).

Understanding the genetic and molecular underpinnings of glioblastoma is crucial for developing effective therapies. Nakase et al. utilized genome-wide polygenic risk scores (PRS) to predict glioma risk and molecular subtypes, demonstrating the potential of PRS in personalizing treatment strategies (ref: Nakase doi.org/10.1093/neuonc/). Hegi et al. reanalyzed data from elderly glioblastoma patients, concluding that those with unmethylated MGMT promoters derive no benefit from temozolomide treatment, highlighting the need for tailored approaches based on genetic markers (ref: Hegi doi.org/10.1093/neuonc/). Kinslow et al. conducted a meta-analysis on the IDH paradox, revealing that while alkylating chemotherapy improves survival in IDH-mutant gliomas, its benefit in IDH-wildtype lower-grade gliomas remains uncertain (ref: Kinslow doi.org/10.1093/neuonc/). Gao et al. explored the impact of brain tumors on glymphatic function, linking tumor characteristics with aquaporin-4 expression and suggesting that glymphatic dysfunction may contribute to glioblastoma pathology (ref: Gao doi.org/10.1158/1078-0432.CCR-24-0150/). Laverty et al. investigated DNA repair mechanisms in TP53-mutant glioblastomas, revealing that elevated homologous recombination and microhomology-mediated end joining activities contribute to treatment resistance (ref: Laverty doi.org/10.1038/s41467-024-49316-8/). Park et al. focused on gene regulatory networks in glioma stem-like cells, demonstrating how these networks influence treatment resistance and tumor recurrence (ref: Park doi.org/10.1126/sciadv.adj7706/). Zhang et al. introduced a novel lipid-polymer nanoparticle for targeted gene editing in glioblastoma vasculature, showcasing innovative approaches to tackle tumor heterogeneity (ref: Zhang doi.org/10.1002/advs.202309314/).

Therapeutic strategies for glioblastoma are increasingly focusing on overcoming drug resistance and improving patient outcomes. Park et al. revisited the incidence of leptomeningeal metastases in IDH-wildtype glioblastomas, finding a high incidence associated with aggressive molecular factors, which underscores the need for vigilant monitoring and tailored treatment approaches (ref: Park doi.org/10.1093/neuonc/). Sloan et al. conducted a Phase I study on the safety of combining ipilimumab and nivolumab in newly diagnosed glioblastoma patients, reporting tolerable toxicity levels and paving the way for future efficacy trials (ref: Sloan doi.org/10.1093/neuonc/). Kinslow et al. also contributed to the understanding of alkylating chemotherapy's effects on IDH-wildtype and -mutant gliomas, reinforcing the need for personalized treatment strategies based on genetic profiles (ref: Kinslow doi.org/10.1093/neuonc/). Peng et al. explored the sequential inhibition of PARP and BET, proposing a rational therapeutic strategy to enhance glioblastoma treatment efficacy (ref: Peng doi.org/10.1002/advs.202307747/). Ganser et al. highlighted the role of mesenchymal glioblastoma stem-like cells in therapy resistance, suggesting that targeting these cells may improve treatment outcomes (ref: Ganser doi.org/10.1002/ijc.35064/). Chantzi et al. evaluated the CUSP9 polypharmaceutical strategy, emphasizing the need for comprehensive assessments of multi-drug regimens to optimize glioblastoma treatment (ref: Chantzi doi.org/10.1016/j.compbiomed.2024.108748/). He et al. examined the activation of the mevalonate pathway in response to anti-cancer treatments, proposing that this metabolic vulnerability could be exploited for therapeutic gain (ref: He doi.org/10.1158/2767-9764.CRC-24-0049/). Liu et al. investigated IMPDH inhibition as a novel therapeutic target, revealing its potential to synergize with chemotherapeutic agents in glioblastoma cells (ref: Liu doi.org/10.3390/ijms25115992/).

Advancements in imaging and diagnostic approaches are crucial for improving glioblastoma management. Noh et al. highlighted the potential of targeting IGF2 to enhance viro-immunotherapy, emphasizing the role of imaging in assessing treatment responses (ref: Noh doi.org/10.1093/neuonc/). Ziegenfeuter et al. addressed the challenge of spatial intratumoral heterogeneity in glioblastoma, utilizing multimodal imaging techniques to differentiate between true tumor progression and pseudoprogression, which is vital for accurate treatment assessment (ref: Ziegenfeuter doi.org/10.1007/s00259-024-06782-y/). Blomquist et al. focused on the sensitivity of glioblastoma to saracatinib in the context of EGFRvIII expression, revealing the importance of molecular imaging in predicting treatment responses (ref: Blomquist doi.org/10.3390/ijms25116279/). Zhao et al. proposed integrating FLAIR imaging with contrast-enhanced imaging to improve prognostic accuracy in IDH-wildtype glioblastomas, indicating that imaging advancements can enhance clinical decision-making (ref: Zhao doi.org/10.3171/2024.4.JNS232658/). Kural et al. explored the mechanistic role of endocytosis in sensitizing cancer cells to apoptosis, suggesting that imaging could aid in understanding cellular responses to therapies (ref: Kural doi.org/10.1038/s41419-024-06822-3/). Sharma et al. investigated the interplay between PRC2 and miR-3189 in regulating EMT in glioblastoma, highlighting the potential of imaging to elucidate molecular interactions within tumors (ref: Sharma doi.org/10.1002/jcp.31326/).

The role of stem cells and tumor heterogeneity is pivotal in understanding glioblastoma biology and treatment resistance. Park et al. examined the gene regulatory network topology in glioma stem-like cells, revealing how these networks govern treatment escape and resistance, which is crucial for developing targeted therapies (ref: Park doi.org/10.1126/sciadv.adj7706/). Ruan et al. introduced a brain-targeted Cas12a ribonucleoprotein nanocapsule for simultaneous gene editing of multiple oncogenes, showcasing a novel approach to tackle glioblastoma heterogeneity (ref: Ruan doi.org/10.1002/advs.202402178/). Chantzi et al. conducted an exhaustive evaluation of the CUSP9 protocol, a polypharmaceutical strategy aimed at addressing the complexity of glioblastoma by targeting multiple pathways (ref: Chantzi doi.org/10.1016/j.compbiomed.2024.108748/). Chakraborty et al. studied KR158 spheres that harbor slow-cycling cells, recapitulating high-grade glioma features and emphasizing the importance of understanding cancer stem cell dynamics in glioblastoma (ref: Chakraborty doi.org/10.3390/cells13110938/). Jiang et al. proposed a novel anti-cancer strategy by reprogramming glioblastoma cells into non-cancerous neuronal cells, highlighting innovative therapeutic avenues (ref: Jiang doi.org/10.3390/cells13110897/). Zhang et al. explored the potential of TRAIL-exosomes derived from induced neural stem cells as a treatment strategy for brain cancer, further emphasizing the therapeutic promise of stem cell-derived products (ref: Zhang doi.org/10.1016/j.jconrel.2024.06.048/).

Clinical outcomes and prognostic factors in glioblastoma are critical for guiding treatment decisions. Arrieta et al. demonstrated that ultrasound-mediated delivery of doxorubicin enhances immune modulation and improves responses to PD-1 blockade, leading to long-term survival in glioma-bearing mice, which underscores the importance of innovative delivery methods in improving clinical outcomes (ref: Arrieta doi.org/10.1038/s41467-024-48326-w/). Suh et al. assessed the status of advance care planning and palliative care in glioblastoma patients, revealing that timely palliative care consultations are associated with less aggressive end-of-life care and longer hospice use, emphasizing the need for integrated care approaches (ref: Suh doi.org/10.1093/oncolo/). Barzegar Behrooz et al. analyzed genetic prognostic factors in adult diffuse gliomas, providing insights into how clinical variables and molecular profiles influence overall survival, which is essential for personalized treatment strategies (ref: Barzegar Behrooz doi.org/10.3390/cancers16112121/). Ortega et al. introduced a hyperspectral imaging dataset for glioblastoma, which could enhance diagnostic capabilities and facilitate the identification of disease patterns (ref: Ortega doi.org/10.1038/s41597-024-03510-x/).

Innovative treatment modalities are essential for improving glioblastoma management. Nakase et al. utilized genome-wide polygenic risk scores to predict glioma risk and molecular subtypes, highlighting the potential for personalized treatment approaches based on genetic susceptibility (ref: Nakase doi.org/10.1093/neuonc/). Park et al. revisited the incidence of leptomeningeal metastases in IDH-wildtype glioblastomas, emphasizing the need for innovative strategies to address this complication (ref: Park doi.org/10.1093/neuonc/). Nakazawa et al. explored the potential of HIF-1α knockout NK cells in enhancing cytotoxicity against glioblastoma cells, suggesting a promising immunotherapeutic alternative (ref: Nakazawa doi.org/10.3390/ijms25115896/). Giannotti et al. investigated the neuroprotective potential of N-methylpyridinium against neuroinflammation, indicating that novel compounds could offer therapeutic benefits in glioblastoma treatment (ref: Giannotti doi.org/10.3390/ijms25116000/).