The tumor microenvironment plays a pivotal role in glioblastoma (GBM) progression and treatment resistance. Pine et al. demonstrated that a neuroanatomically accurate human microenvironment is essential for maintaining the cellular states found in primary GBMs, highlighting the limitations of current tumor models in replicating these states (ref: Pine doi.org/10.1158/2159-8290.CD-20-0057/). Myeloid-derived suppressor cells (MDSCs) are crucial in modulating immune responses in GBM, with Bayik et al. revealing that distinct subsets of MDSCs exhibit sex-specific roles in tumor growth, with monocytic MDSCs predominating in male tumors and granulocytic MDSCs in female blood (ref: Bayik doi.org/10.1158/2159-8290.CD-19-1355/). Furthermore, Sarkar et al. explored the potential of niacin to reactivate dysfunctional myeloid cells, suggesting a novel therapeutic avenue for enhancing antitumor immunity (ref: Sarkar doi.org/10.1126/scitranslmed.aay9924/). Maas et al. provided insights into how GBM hijacks microglial gene expression to support its growth, indicating that microglia in the tumor microenvironment downregulate genes critical for tumor recognition and destruction (ref: Maas doi.org/10.1186/s12974-020-01797-2/). Lastly, Ji et al. investigated the epigenetic regulation of long non-coding RNAs (lncRNAs) in GBM, revealing their potential as biomarkers for understanding tumor biology (ref: Ji doi.org/10.3892/ijmm.2020.4579/).

Therapeutic strategies for glioblastoma (GBM) face significant challenges due to inherent drug resistance mechanisms. Taylor et al. reported that Actinomycin D effectively downregulates Sox2, a key stemness factor, improving survival in preclinical models of recurrent GBM (ref: Taylor doi.org/10.1093/neuonc/). The OPARATIC trial by Hanna et al. assessed the pharmacokinetics of olaparib in combination with temozolomide, revealing poor brain penetration of olaparib, which limits its efficacy despite its potential to enhance treatment responses (ref: Hanna doi.org/10.1093/neuonc/). Bhat et al. demonstrated that 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine preserves cognitive function post-irradiation in mouse models, suggesting a potential for improving patient quality of life during treatment (ref: Bhat doi.org/10.1093/neuonc/). Hua et al. emphasized the need to target mesenchymal-type GBMs, which are associated with aggressive behavior and treatment resistance, to improve patient outcomes (ref: Hua doi.org/10.1038/s12276-020-0413-1/). Wang et al. identified the CXCL12/CXCR4 axis as a mediator of temozolomide resistance, proposing that targeting this pathway could enhance treatment efficacy (ref: Wang doi.org/10.1016/j.jns.2020.116837/).

Understanding the molecular mechanisms underlying glioblastoma (GBM) pathogenesis is crucial for developing effective therapies. Bohm et al. utilized PDGF-AA and p53-null neural progenitors to model GBM initiation, revealing insights into the genomic architecture of the disease (ref: Bohm doi.org/10.1093/neuonc/). Nguyen et al. explored the role of histone deacetylase (HDAC) inhibitors in metabolic reprogramming of GBM, demonstrating that these agents can disrupt Warburg effect-related super-enhancers, potentially offering a therapeutic strategy (ref: Nguyen doi.org/10.1172/JCI129049/). Kant et al. highlighted the significance of fatty acid oxidation in GBM, suggesting that targeting metabolic pathways could lead to synthetic lethality in treatment-resistant tumors (ref: Kant doi.org/10.1038/s41419-020-2449-5/). Hatcher et al. investigated the pathogenesis of peritumoral hyperexcitability in a CRISPR-based model, shedding light on the cellular mechanisms contributing to seizures associated with GBM (ref: Hatcher doi.org/10.1172/JCI133316/). Maas et al. reiterated the importance of microglial gene expression modulation in supporting GBM growth, emphasizing the tumor's ability to manipulate its microenvironment (ref: Maas doi.org/10.1186/s12974-020-01797-2/).

Advancements in modeling glioblastoma (GBM) are essential for understanding tumor behavior and testing new therapies. Krieger et al. developed a human cerebral organoid model to study GBM invasion, providing a more accurate representation of tumor dynamics compared to traditional models (ref: Krieger doi.org/10.1093/neuonc/). Press et al. analyzed the timing of chemoradiotherapy post-surgery, revealing that optimal timing can significantly impact patient outcomes, particularly when stratified by prognostic classifications (ref: Press doi.org/10.1002/cncr.32797/). Meneceur et al. established patient-derived xenografts to better reflect human GBM characteristics, which are crucial for preclinical testing of novel therapies (ref: Meneceur doi.org/10.3390/cancers12040871/). Cluceru et al. focused on differentiating treatment-induced effects from recurrent tumors using MRI, which is vital for accurate patient management (ref: Cluceru doi.org/10.1093/neuonc/). Zhang et al. reviewed the role of circular RNAs in glioma, suggesting their potential as biomarkers and therapeutic targets (ref: Zhang doi.org/10.3892/ijo.2020.5049/).

Genetic and epigenetic factors play a significant role in glioblastoma (GBM) development and treatment response. Hatcher et al. examined the pathogenesis of peritumoral hyperexcitability, linking genetic alterations to seizure activity in GBM patients, which could inform therapeutic strategies (ref: Hatcher doi.org/10.1172/JCI133316/). Zhang et al. provided a comprehensive review of circular RNAs in glioma, emphasizing their involvement in tumor progression and potential as therapeutic targets (ref: Zhang doi.org/10.3892/ijo.2020.5049/). Weenink et al. discussed the limitations of current immunotherapy approaches in GBM, highlighting the need for a better understanding of genetic factors that influence treatment efficacy (ref: Weenink doi.org/10.3390/cancers12030751/). These studies collectively underscore the complexity of GBM genetics and epigenetics, suggesting that integrated approaches targeting these factors may enhance therapeutic outcomes.

Clinical outcomes in glioblastoma (GBM) are influenced by various factors, including treatment access and immune response. Crommentuijn et al. investigated the immune involvement of the contralateral hemisphere in a GBM mouse model, suggesting that immune checkpoint blockade could activate immune responses both locally and distally, potentially targeting infiltrating tumor cells (ref: Crommentuijn doi.org/10.1136/jitc-2019-000323/). Lin et al. compared survival rates among glioma patients in the US Military Health System with those in the Surveillance, Epidemiology, and End Results program, revealing a survival advantage linked to universal healthcare access (ref: Lin doi.org/10.1002/cncr.32884/). Li et al. introduced PreMSIm, an R package for predicting microsatellite instability, which could aid in identifying patients likely to respond to immunotherapy (ref: Li doi.org/10.1016/j.csbj.2020.03.007/). Ramakrishna et al. provided guidance for prioritizing neuro-oncologic cases during the COVID-19 pandemic, emphasizing the need for resource allocation strategies (ref: Ramakrishna doi.org/10.1007/s11060-020-03488-7/). Marx et al. explored GD2 targeting as a promising immunotherapeutic approach against malignant glioma, highlighting the potential for enhanced treatment efficacy (ref: Marx doi.org/10.1007/s11060-020-03470-3/).

Innovative therapeutic approaches are crucial for improving outcomes in glioblastoma (GBM) treatment. Zhang et al. reviewed the role of circular RNAs in glioma, emphasizing their potential as biomarkers and therapeutic targets due to their involvement in tumor progression (ref: Zhang doi.org/10.3892/ijo.2020.5049/). Wang et al. identified the CXCL12/CXCR4 axis as a key player in mediating temozolomide resistance, suggesting that targeting this pathway could enhance treatment responses in resistant GBM cells (ref: Wang doi.org/10.1016/j.jns.2020.116837/). Papale et al. discussed the impact of hypoxia, inflammation, and necrosis on cancer stem cell progression in GBM, indicating that these factors could be targeted to disrupt tumor growth (ref: Papale doi.org/10.3390/ijms21082660/). Xu et al. investigated the role of lncRNA MIR4435-2HG in promoting GBM cell proliferation and invasion, proposing that modulation of this lncRNA could serve as a therapeutic strategy (ref: Xu doi.org/10.1111/jcmm.15280/). These studies highlight the need for innovative approaches that address the complex biology of GBM to improve patient outcomes.