Glioblastoma (GBM) is characterized by significant cell state plasticity, which contributes to therapeutic resistance and tumor progression. Recent studies have highlighted the role of BRD2 in regulating NF-κB-mediated mesenchymal transition, suggesting that targeting this pathway may enhance therapy response (ref: Vadla doi.org/10.1093/neuonc/). Additionally, Bourmeau et al. utilized fluorescent reporters to monitor the plasticity of proneural and mesenchymal subtypes in real-time, revealing that hybrid glioblastoma cells exhibit resistance to therapy and are dependent on nuclear import mechanisms (ref: Bourmeau doi.org/10.1093/neuonc/). Doroszko et al. further elucidated the relationship between GBM cell differentiation states and invasion routes, identifying biomarkers that could be targeted to modulate invasive cell states (ref: Doroszko doi.org/10.1038/s41467-025-61999-1/). Liu's research identified a metabolic-epigenetic axis involving the mitochondrial calcium uniporter that supports glioblastoma stem cell survival, indicating potential vulnerabilities for therapeutic targeting (ref: Liu doi.org/10.1158/0008-5472.CAN-25-0419/). Overall, these studies underscore the complexity of GBM plasticity and the need for innovative strategies to overcome therapeutic resistance.

The development of effective therapeutic strategies for glioblastoma (GBM) has been a focus of recent research, with various approaches being explored. Breen et al. conducted a Phase II trial assessing the efficacy of dasatinib in combination with chemoradiotherapy, establishing a maximum tolerated dose and enrolling 204 patients, although the results on overall survival remain to be fully analyzed (ref: Breen doi.org/10.1093/neuonc/). Wang et al. introduced a modular protein-based nanocarrier system that enhances drug delivery efficacy across the blood-brain barrier, demonstrating improved loading capacity for hydrophobic small molecules (ref: Wang doi.org/10.1002/anie.202503085/). Cheng et al. developed a sequential-targeting sonodynamic nanovaccine that activates local and systemic immunity against GBM, showing promise in overcoming the immunosuppressive tumor microenvironment (ref: Cheng doi.org/10.1021/acsnano.5c08928/). Moreover, Tang et al. analyzed the impact of peri-tumoral resection on survival outcomes in GBM patients, highlighting the potential benefits of extending surgical resection beyond contrast-enhancing tumor areas (ref: Tang doi.org/10.1002/cncr.70016/). Collectively, these studies reflect a multifaceted approach to GBM treatment, emphasizing the importance of combining surgical, pharmacological, and immunotherapeutic strategies.

The tumor microenvironment (TME) plays a crucial role in glioblastoma (GBM) progression and immune evasion. Rossari et al. explored the use of tumor-targeted cytokines to enhance CAR T cell activity, demonstrating that localized delivery can rescue T cell function in the immunosuppressive TME (ref: Rossari doi.org/10.1126/scitranslmed.ado9511/). Shifman et al. investigated the role of autophagy in GBM, showing that targeting autophagy pathways can remodel the TME and improve survival outcomes (ref: Shifman doi.org/10.1186/s13046-025-03473-w/). Sahoo et al. reported on the adaptive quasi-quiescence of GBM cells in response to engineered emulsion matrices, indicating a survival strategy that may complicate treatment efforts (ref: Sahoo doi.org/10.1002/adhm.202501637/). Additionally, Xiong et al. demonstrated that targeting CSPG4 enhances the anti-tumor activity of CAR-NK cells, suggesting a novel immunotherapeutic strategy to overcome TME-induced resistance (ref: Xiong doi.org/10.1007/s13402-025-01095-0/). These findings highlight the dynamic interplay between GBM cells and their microenvironment, emphasizing the need for targeted therapies that can effectively disrupt immune evasion mechanisms.

Genetic and epigenetic alterations are pivotal in glioblastoma (GBM) pathogenesis and treatment response. Costa et al. identified a new hypermethylation phenotype associated with astrocyte-like cell states in IDH-wildtype GBM, suggesting that DNA methylation patterns could serve as biomarkers for tumor classification and therapeutic targeting (ref: Costa doi.org/10.1186/s13059-025-03670-y/). Su et al. explored the synergistic effects of linagliptin and cPLA2 inhibition on temozolomide efficacy, revealing a complex interplay between metabolic pathways and drug resistance mechanisms (ref: Su doi.org/10.1016/j.apsb.2025.05.012/). Zhou et al. presented an innovative approach for generating CAR macrophages in vivo using enucleated mesenchymal stem cells, which may enhance the effectiveness of immunotherapies in GBM (ref: Zhou doi.org/10.1073/pnas.2426724122/). Wang et al. utilized advanced proteomic techniques to uncover novel pathological mechanisms in glioma, paving the way for precision therapy based on specific protein expressions (ref: Wang doi.org/10.1016/j.cellin.2025.100253/). These studies underscore the importance of understanding genetic and epigenetic factors in developing targeted therapies for GBM.

Innovative imaging and surgical techniques are transforming the management of glioblastoma (GBM). Jost-Engl et al. demonstrated that an intensive exercise intervention during chemotherapy can enhance cardiorespiratory fitness and quality of life in high-grade glioma patients, suggesting that supportive care can play a critical role in treatment outcomes (ref: Jost-Engl doi.org/10.1093/neuonc/). Laviv et al. reported on the use of fluorescence-guided resection with 5-aminolevulinic acid, which significantly improved the extent of resection and overall survival in patients with subventricular zone GBM (ref: Laviv doi.org/10.3171/2025.3.JNS242570/). Yu et al. explored phosphatidylcholine-derived carriers for drug delivery, showing that these carriers can enhance therapeutic efficacy while minimizing cytotoxicity (ref: Yu doi.org/10.1016/j.jconrel.2025.113999/). Bhalla et al. combined fluorescence-guided multiple sampling with spatial-omics to capture the intratumor heterogeneity of GBM, providing insights into tumor biology that could inform personalized treatment strategies (ref: Bhalla doi.org/10.1158/1541-7786.MCR-25-0194/). These advancements illustrate the potential for integrating innovative techniques to improve surgical outcomes and patient care in GBM.

Clinical outcomes and prognostic factors in glioblastoma (GBM) have been extensively studied to improve patient management. Sferruzza et al. assessed time-trend bias in GBM prognosis over two decades, revealing that outcomes for newly diagnosed patients treated with the standard Stupp protocol have evolved, which may influence future clinical trial designs (ref: Sferruzza doi.org/10.1093/neuonc/). Tang et al. analyzed the impact of peri-tumoral resection on survival, finding that extending resection beyond contrast-enhancing areas can significantly improve patient outcomes (ref: Tang doi.org/10.1002/cncr.70016/). Liu et al. identified a metabolic-epigenetic axis that maintains glioblastoma stem cells, suggesting that targeting these pathways could enhance treatment efficacy and patient survival (ref: Liu doi.org/10.1158/0008-5472.CAN-25-0419/). Seo et al. focused on the role of DHRS13 in maintaining the undifferentiated state of glioblastoma cells, indicating that this protein could serve as a potential therapeutic target (ref: Seo doi.org/10.1038/s41467-025-62148-4/). These findings emphasize the importance of identifying prognostic factors and optimizing treatment strategies to improve clinical outcomes in GBM.

Nanotechnology and drug delivery systems are at the forefront of glioblastoma (GBM) research, aiming to enhance therapeutic efficacy and minimize side effects. Sacchi et al. investigated a phosphoserine phosphatase variant in Alzheimer's disease patients, highlighting the potential for targeting metabolic pathways in GBM therapy (ref: Sacchi doi.org/10.1111/febs.70169/). Wang et al. utilized 4D label-free proteomics to uncover novel mechanisms in glioma, paving the way for precision therapy based on specific protein expressions (ref: Wang doi.org/10.1016/j.cellin.2025.100253/). Zhou et al. developed a method for in vivo generation of CAR macrophages using enucleated mesenchymal stem cells, which could streamline the production of effective immunotherapies for GBM (ref: Zhou doi.org/10.1073/pnas.2426724122/). Sahoo et al. demonstrated that engineered emulsion matrices can promote adaptive survival in glioblastoma cells, indicating a need for innovative delivery systems that can overcome tumor resilience (ref: Sahoo doi.org/10.1002/adhm.202501637/). These studies illustrate the transformative potential of nanotechnology in improving drug delivery and therapeutic outcomes in GBM.

Metabolic reprogramming is a critical aspect of glioblastoma (GBM) biology, influencing tumor growth and treatment resistance. Boulifa et al. demonstrated that CD44v6-CAR-NK92 cells exhibit specific cytotoxicity against GBM, highlighting the potential of targeting metabolic pathways in immunotherapy (ref: Boulifa doi.org/10.1186/s12935-025-03865-0/). Kalitin et al. explored the effects of LCS1269 on GBM cell death, revealing that despite activating DNA damage response pathways, GBM cells remain susceptible to treatment, suggesting a complex interplay between metabolic signaling and therapeutic efficacy (ref: Kalitin doi.org/10.3390/ijms26136014/). Additionally, de São José et al. investigated a synergistic combination of a quinoxaline-based and a PI3K/mTOR dual inhibitor, emphasizing the need for innovative pharmacologic approaches to combat GBM's aggressive nature (ref: de São José doi.org/10.3390/ijms26136392/). These findings underscore the importance of understanding metabolic reprogramming in developing effective therapeutic strategies for GBM.