The tumor microenvironment (TME) plays a crucial role in the progression and treatment resistance of glioblastoma (GBM). Recent studies have highlighted the dynamic interactions between tumor cells and immune components within the TME. Hoogstrate et al. conducted a comprehensive transcriptome analysis of glioblastoma, revealing that transcriptional subtypes form an interconnected continuum, which may inform treatment strategies (ref: Hoogstrate doi.org/10.1016/j.ccell.2023.02.019/). Goenka et al. focused on the oncogenic long noncoding RNA LINC02283, demonstrating its enhancement of PDGF receptor A-mediated signaling, which drives glioblastoma tumorigenesis, indicating a potential therapeutic target (ref: Goenka doi.org/10.1093/neuonc/). Yang et al. explored polio virotherapy, showing that it targets the malignant glioma myeloid infiltrate, suggesting that myeloid cells contribute significantly to immune suppression and tumor progression (ref: Yang doi.org/10.1093/neuonc/). Kesarwani et al. identified quinolinate as a metabolic node promoting immune tolerance in glioblastoma, emphasizing the role of tryptophan metabolism in immune evasion (ref: Kesarwani doi.org/10.1038/s41467-023-37170-z/). Furthermore, Zhang et al. developed STING agonist-loaded nanoparticles that enhance antitumor immunity and radiotherapy efficacy, highlighting innovative approaches to overcome immune resistance (ref: Zhang doi.org/10.1038/s41467-023-37328-9/). Rajendran et al. utilized single-cell RNA sequencing to reveal immunosuppressive myeloid cell diversity during malignant progression, underscoring the complexity of the TME in gliomas (ref: Rajendran doi.org/10.1016/j.celrep.2023.112197/). Collectively, these studies underscore the intricate interplay between glioblastoma cells and the immune landscape, suggesting that targeting these interactions may enhance therapeutic outcomes.

Innovative therapeutic strategies and drug delivery systems are pivotal in enhancing the treatment efficacy for glioblastoma (GBM). Zhao et al. introduced a novel organic assembly designed for blood-brain barrier (BBB) crossing, achieving significant tumor accumulation and effective imaging capabilities, which could facilitate targeted therapies (ref: Zhao doi.org/10.1002/adma.202208097/). Zhang et al. further advanced this concept by cloaking gold nanorods with GBM patient-derived tumor cell membranes, demonstrating enhanced BBB penetration and selective targeting of GBM cells, which is crucial for precise surgical interventions (ref: Zhang doi.org/10.1021/jacs.2c13701/). Jain et al. identified cancer-associated fibroblasts (CAFs) in glioblastoma, suggesting their protumoral effects and potential as therapeutic targets (ref: Jain doi.org/10.1172/JCI147087/). Dong et al. explored the combination of anti-VEGF therapy with CAR-T cell delivery, showing improved efficacy in GBM models, highlighting the importance of vascular normalization in immunotherapy (ref: Dong doi.org/10.1136/jitc-2022-005583/). Additionally, Fuentes-Fayos et al. reported that combining metformin and simvastatin yielded additive antitumor effects, indicating metabolic drugs' potential in GBM treatment (ref: Fuentes-Fayos doi.org/10.1016/j.ebiom.2023.104484/). These studies collectively emphasize the need for innovative drug delivery systems and combination therapies to overcome the challenges posed by GBM's aggressive nature and treatment resistance.

Understanding the molecular mechanisms underlying glioblastoma (GBM) is essential for developing effective therapies. Qiu et al. identified USP10 as a key deubiquitinating enzyme that promotes the proneural-to-mesenchymal transition in GBM by stabilizing RUNX1, suggesting that targeting this pathway may inhibit aggressive tumor behavior (ref: Qiu doi.org/10.1038/s41419-023-05734-y/). Li et al. demonstrated that temozolomide treatment downregulates SOX4 via the LINC00470-mediated transcription factor EGR2, highlighting a potential mechanism of action for this standard therapy (ref: Li doi.org/10.1111/cns.14181/). Silginer et al. investigated the MET signaling pathway's role in radiotherapy resistance, revealing that MET inhibition does not sensitize glioma cells to irradiation, which poses challenges for combinatorial treatment strategies (ref: Silginer doi.org/10.1186/s40478-023-01527-8/). Ladenhauf et al. correlated peritumoral ADC values with MGMT methylation status, providing insights into imaging biomarkers that may predict treatment responses (ref: Ladenhauf doi.org/10.3390/cancers15051384/). Ciechomska et al. emphasized the heterogeneity of GBM through patient-derived cell cultures, which can facilitate the exploration of novel therapeutic opportunities (ref: Ciechomska doi.org/10.3390/cancers15051562/). These findings illustrate the complex genetic landscape of GBM and underscore the importance of targeting specific molecular pathways to improve treatment outcomes.

Cancer stem cells (CSCs) play a critical role in glioblastoma (GBM) heterogeneity and treatment resistance. Tritz et al. demonstrated that anti-PD-1 therapy combined with extended half-life IL2 can synergize to treat murine glioblastoma, independent of host MHC Class I expression, indicating a potential strategy to enhance immunotherapy efficacy (ref: Tritz doi.org/10.1158/2326-6066.CIR-22-0570/). Fukasawa et al. identified the MEK5-ERK5 signaling axis as crucial for maintaining glioma stem cell self-renewal and tumorigenicity, suggesting that targeting this pathway could improve therapeutic strategies against GBM (ref: Fukasawa doi.org/10.1158/2767-9764.CRC-22-0243/). Starr et al. optimized chimeric antigen receptor (CAR) T cell therapy targeting IL13Rα2, enhancing selectivity and functionality, which is vital for minimizing off-tumor effects (ref: Starr doi.org/10.1158/2767-9764.CRC-22-0185/). He et al. quantitatively evaluated stem-like markers in GBM using single-cell RNA sequencing, providing insights into the efficiency of various targeting methods (ref: He doi.org/10.3390/cancers15051557/). Ciechomska et al. reiterated the importance of understanding GBM heterogeneity through patient-derived cultures, which can inform the development of targeted therapies (ref: Ciechomska doi.org/10.3390/cancers15051562/). These studies collectively highlight the significance of CSCs in GBM and the need for tailored therapeutic approaches to address tumor heterogeneity.

Immunotherapy, particularly checkpoint inhibition, has emerged as a promising strategy for glioblastoma (GBM) treatment. Tritz et al. demonstrated that anti-PD-1 therapy combined with extended half-life IL2 can effectively treat murine GBM, suggesting a potential avenue for enhancing immune responses against this malignancy (ref: Tritz doi.org/10.1158/2326-6066.CIR-22-0570/). Celesti et al. explored protective anti-tumor vaccination strategies targeting the MHC class II transactivator CIITA, emphasizing the need for novel immunological approaches to improve patient outcomes in GBM (ref: Celesti doi.org/10.3389/fimmu.2023.1133177/). Gu et al. investigated third-generation CAR-T cells targeting IL13Rα2, finding that specific transmembrane domains enhance anti-glioblastoma efficacy, which is crucial for optimizing CAR-T cell therapy (ref: Gu doi.org/10.1007/s00262-023-03423-5/). Tręda et al. reported that tyrosine kinase inhibitors can increase EGFRvIII epitope accessibility, creating more opportunities for immunotherapy, highlighting the interplay between targeted therapies and immunological strategies (ref: Tręda doi.org/10.3390/ijms24054350/). These findings underscore the potential of combining immunotherapy with other treatment modalities to overcome the challenges posed by GBM.

Radiotherapy remains a cornerstone in glioblastoma (GBM) treatment, and recent studies have focused on enhancing its efficacy through combination therapies. Li et al. demonstrated that combining radiotherapy with anlotinib significantly improves therapeutic outcomes in GBM, suggesting a synergistic effect that warrants further clinical exploration (ref: Li doi.org/10.1016/j.radonc.2023.109633/). Silginer et al. assessed the role of the MET signaling pathway in radiotherapy resistance, revealing that MET inhibition does not sensitize glioma cells to irradiation, which poses challenges for combinatorial treatment strategies (ref: Silginer doi.org/10.1186/s40478-023-01527-8/). Teske et al. investigated volumetric MRI changes in GBM patients, finding that new contrast-enhancement volumes can serve as prognostic indicators between surgery and the initiation of adjuvant therapy, which is crucial for treatment planning (ref: Teske doi.org/10.3390/cancers15061745/). Vottero et al. explored the molecular mode of action of gatastatin, a γ-tubulin-specific inhibitor, proposing a novel therapeutic strategy targeting GBM (ref: Vottero doi.org/10.3390/cancers15061714/). Bouzos et al. developed sandwich culture platforms to study cancer cell migration, providing insights into the mechanical properties influencing GBM progression (ref: Bouzos doi.org/10.3390/cancers15061729/). These studies collectively highlight the importance of combining radiotherapy with novel agents and understanding the underlying mechanisms to improve GBM treatment outcomes.

Identifying biomarkers and prognostic indicators is essential for improving glioblastoma (GBM) management. Ding et al. developed a novel exosome-related risk signature that can independently predict patient prognosis and response to anti-PD-1 immunotherapy, highlighting the potential of exosomal biomarkers in clinical applications (ref: Ding doi.org/10.3389/fimmu.2023.1071023/). Wang et al. focused on circXPO1, a circular RNA significantly upregulated in GBM, suggesting its role in malignancy and potential as a therapeutic target (ref: Wang doi.org/10.3390/cells12060831/). Ladenhauf et al. correlated peritumoral ADC values with MGMT methylation status, providing insights into imaging biomarkers that may predict treatment responses (ref: Ladenhauf doi.org/10.3390/cancers15051384/). Wanis et al. conducted a population-based cohort study to assess the influence of ethnicity on survival from malignant primary brain tumors, revealing disparities that could inform personalized treatment approaches (ref: Wanis doi.org/10.3390/cancers15051464/). These findings underscore the importance of integrating biomarker research into clinical practice to enhance prognostic accuracy and tailor treatment strategies for GBM patients.

The development of novel therapeutic agents and approaches is critical for addressing the challenges posed by glioblastoma (GBM). Lin et al. investigated the anticancer activities of Antrodia salmonea, demonstrating its ability to inhibit metastasis and induce apoptotic and autophagic cell death in GBM cells, suggesting its potential as a therapeutic agent (ref: Lin doi.org/10.1016/j.biopha.2022.114178/). Araujo-Abad et al. explored glioblastoma-derived small extracellular vesicles as nanoparticles for glioma treatment, emphasizing the need for more efficient drug delivery systems to mitigate side effects associated with high-dose therapies (ref: Araujo-Abad doi.org/10.3390/ijms24065910/). Lee et al. designed brain-targeted exosome-mimetic cell membrane nanovesicles to enhance the delivery of therapeutic oligonucleotides into the brain, showcasing a promising approach for treating brain tumors (ref: Lee doi.org/10.1002/btm2.10426/). Sun et al. reported on ultrasound-mediated delivery of flexibility-tunable polymer drug conjugates, which could improve the efficacy of chemotherapy for GBM by enhancing drug transport across the blood-brain barrier (ref: Sun doi.org/10.1002/btm2.10408/). These studies highlight the ongoing efforts to innovate therapeutic strategies and improve drug delivery methods to enhance treatment outcomes for GBM patients.