Recent advancements in targeted therapies and drug delivery systems for glioblastoma have shown promising results. A study by Wen et al. demonstrated that the combination of dabrafenib and trametinib yielded a 33% objective response rate in high-grade glioma patients, with notable complete and partial responses (ref: Wen doi.org/10.1016/S1470-2045(21)00578-7/). Jiang et al. introduced cation-free siRNA micelles that effectively loaded temozolomide (TMZ) and targeted the STAT3 gene, which is implicated in TMZ resistance, showcasing a robust platform for glioblastoma treatment (ref: Jiang doi.org/10.1002/adma.202104779/). Furthermore, Ang et al. provided insights into nanoparticle trafficking into glioblastoma cells, revealing that ligand-modified nanoparticles could traverse the blood-brain barrier and enhance antitumor effects through metronomic chemotherapy (ref: Ang doi.org/10.1002/adma.202106194/). The efficacy of selinexor, an exportin-1 inhibitor, was evaluated in recurrent glioblastoma, showing promising intratumoral penetration and safety (ref: Lassman doi.org/10.1158/1078-0432.CCR-21-2225/). Additionally, Kim et al. explored the potential of chimeric antigen receptor T cells targeting IL13Rα2, demonstrating their ability to suppress malignant glioma in preclinical models (ref: Kim doi.org/10.3389/fimmu.2021.715000/). Wang et al. highlighted the role of CD73-positive extracellular vesicles in promoting glioblastoma immunosuppression, suggesting a novel therapeutic target (ref: Wang doi.org/10.1038/s41419-021-04359-3/).

The interplay between immunotherapy and the tumor microenvironment in glioblastoma has been a focal point of recent research. Lee et al. investigated the effects of neoadjuvant PD-1 blockade, revealing that while T cell and conventional dendritic cell activation occurred, the immunosuppressive effects of tumor-associated macrophages persisted, limiting overall efficacy (ref: Lee doi.org/10.1038/s41467-021-26940-2/). Perlman et al. introduced a novel imaging technique using magnetic resonance fingerprinting to quantitatively assess apoptosis following oncolytic virotherapy, providing a non-invasive method to monitor therapeutic responses (ref: Perlman doi.org/10.1038/s41551-021-00809-7/). Kenchappa et al. identified atypical protein kinase Cι as an oncogenic driver in glioblastoma, suggesting that targeting this pathway could enhance immunotherapeutic strategies (ref: Kenchappa doi.org/10.1016/j.celrep.2021.110054/). The systematic review by Andrews et al. on BRAFV600 mutations in gliomas emphasized the potential for BRAF inhibitors in targeted therapy, although the clinical implications remain to be fully elucidated (ref: Andrews doi.org/10.1093/neuonc/). Mahlokozera et al. explored the regulatory mechanisms of SOX2 in glioblastoma stem cells, highlighting the role of E3 ligases in maintaining tumorigenicity and treatment resistance (ref: Mahlokozera doi.org/10.1038/s41467-021-26653-6/).

Understanding the molecular mechanisms and identifying biomarkers in glioblastoma are critical for improving patient outcomes. The systematic review by Andrews et al. provided detailed prevalence estimates of BRAFV600 mutations, revealing significant treatment responses to BRAF inhibitors in mutant gliomas (ref: Andrews doi.org/10.1093/neuonc/). Matteoni et al. investigated the cytotoxic effects of chlorpromazine, demonstrating its potential to induce autophagy through endoplasmic reticulum stress, thus presenting a novel repurposing strategy for glioblastoma treatment (ref: Matteoni doi.org/10.1186/s13046-021-02144-w/). Du et al. introduced a polymer-conjugated temozolomide intermediate that responds to visible light and glutathione, enhancing drug delivery and stability in TMZ-resistant glioblastoma (ref: Du doi.org/10.1021/acsami.1c16962/). Hong et al. constructed a competing endogenous RNA network to identify biomarkers with prognostic significance, providing insights into the molecular pathways involved in glioblastoma (ref: Hong doi.org/10.21037/atm-21-4925/). Sun et al. demonstrated that PDRG1 promotes GBM cell proliferation and migration via the MEK/ERK/CD44 pathway, suggesting its potential as a therapeutic target (ref: Sun doi.org/10.1111/cas.15214/). Kim et al. explored the anticancer effects of veratramine, revealing its action through the PI3K/mTOR pathway, further emphasizing the need for novel therapeutic agents in glioblastoma (ref: Kim doi.org/10.1016/j.lfs.2021.120170/).

Nanotechnology and advanced imaging techniques are revolutionizing glioblastoma diagnosis and treatment. Perlman et al. showcased a novel magnetic resonance fingerprinting technique that allows for rapid detection of apoptotic responses to oncolytic virotherapy, enhancing the monitoring of treatment efficacy (ref: Perlman doi.org/10.1038/s41551-021-00809-7/). Ang et al. provided insights into nanoparticle trafficking in glioblastoma, demonstrating that ligand-modified nanoparticles can effectively cross the blood-brain barrier and enhance the effects of metronomic chemotherapy (ref: Ang doi.org/10.1002/adma.202106194/). Li et al. introduced neodymium-coordinated black phosphorus quantum dots, which exhibit promising optoelectronic properties for glioblastoma diagnosis and therapy (ref: Li doi.org/10.1002/smll.202105160/). Zhang et al. presented a hypocrellin-based assembly for sonodynamic therapy, highlighting its potential for non-invasive treatment of glioblastoma (ref: Zhang doi.org/10.1039/d1tb01886h/). Du et al. further advanced drug delivery systems by developing a polymer-conjugated temozolomide intermediate that responds to specific stimuli, enhancing therapeutic efficacy in glioblastoma (ref: Du doi.org/10.1021/acsami.1c16962/).

Chemoresistance remains a significant challenge in glioblastoma treatment, with recent studies exploring underlying mechanisms and potential therapeutic strategies. Wang et al. identified CD73-positive extracellular vesicles that promote immunosuppression in glioblastoma, suggesting a novel target for overcoming chemoresistance (ref: Wang doi.org/10.1038/s41419-021-04359-3/). Xiao et al. developed a ferroptosis-related prognostic risk score model, demonstrating its utility in predicting overall survival and progression-free survival in glioblastoma patients, highlighting the role of ferroptosis in tumor biology (ref: Xiao doi.org/10.1155/2021/). Sun et al. elucidated the role of PDRG1 in promoting GBM cell proliferation and migration through the MEK/ERK/CD44 pathway, indicating its potential as a therapeutic target (ref: Sun doi.org/10.1111/cas.15214/). Chebil et al. conducted an epidemiological study on primary brain tumors, providing insights into incidence rates and survival trends, which are crucial for understanding treatment outcomes (ref: Chebil doi.org/10.1159/000519512/). Bunevicius et al. explored the impact of tumor genetic profiles on stereotactic radiosurgery outcomes, emphasizing the importance of personalized treatment approaches in glioblastoma management (ref: Bunevicius doi.org/10.3171/2021.7.JNS211277/).

Clinical trials are essential for evaluating new treatment strategies in glioblastoma. Bota et al. reported on a phase I/II trial assessing marizomib, a pan-proteasome inhibitor, demonstrating its safety and preliminary efficacy in recurrent glioblastoma (ref: Bota doi.org/10.1093/noajnl/). Roh et al. introduced a novel biguanide (IM1761065) that inhibited bioenergetics in glioblastoma tumorspheres, suggesting a new avenue for therapeutic intervention (ref: Roh doi.org/10.1007/s11060-021-03903-7/). Garcia et al. highlighted the prevalence of hematological adverse events during glioblastoma management, providing insights into treatment-related complications (ref: Garcia doi.org/10.1007/s11060-021-03891-8/). Werlenius et al. conducted a randomized phase II trial evaluating the immunotherapy ALECSAT in conjunction with standard treatment, revealing its potential to enhance therapeutic outcomes (ref: Werlenius doi.org/10.1093/noajnl/). Langston et al. presented a case report on primary glioblastoma of the cauda equina, contributing to the understanding of rare glioblastoma presentations (ref: Langston doi.org/10.1093/noajnl/).

Genetic and epigenetic factors play a crucial role in glioblastoma progression and treatment response. Lu et al. performed integrative analyses to establish the prognostic significance of RCN1, developing a predictive model for overall survival in glioblastoma patients (ref: Lu doi.org/10.3389/fmolb.2021.736947/). Huang et al. identified GSTM1 as a prognostic marker through chromatin accessibility analysis, highlighting its potential as a therapeutic target (ref: Huang doi.org/10.1186/s13148-021-01181-8/). Okada et al. demonstrated that folate metabolism is selectively cytotoxic to glioma stem cells, suggesting that targeting this pathway could improve treatment outcomes (ref: Okada doi.org/10.3390/ijms222111633/). Chen et al. introduced the C-Circle biomarker as a blood-based diagnostic for alternative-lengthening-of-telomeres activity, providing a novel approach for glioblastoma diagnosis (ref: Chen doi.org/10.3390/cancers13215369/). Pagano et al. explored the role of tau in glioblastoma progression, revealing its impact on cell organization and signaling pathways (ref: Pagano doi.org/10.3390/cancers13225818/).

Emerging therapies and novel approaches are critical in the fight against glioblastoma. Su et al. investigated the role of NOX4-derived ROS in regulating FOXM1 expression and aerobic glycolysis, suggesting a potential therapeutic target for metabolic reprogramming in glioblastoma (ref: Su doi.org/10.1186/s12885-021-08933-y/). Kim et al. evaluated the anticancer effects of veratramine, demonstrating its action through the PI3K/mTOR signaling pathway, indicating its potential as a therapeutic agent (ref: Kim doi.org/10.1016/j.lfs.2021.120170/). Zhang et al. presented a hypocrellin-based assembly for sonodynamic therapy, emphasizing its non-invasive treatment potential for glioblastoma (ref: Zhang doi.org/10.1039/d1tb01886h/). Leroy et al. proposed a standardized procedure for interstitial photodynamic therapy, aiming to enhance clinical applications in glioblastoma treatment (ref: Leroy doi.org/10.3390/cancers13225754/). Clavreul et al. identified preoperative blood count parameters that correlate with prognosis in IDH-wildtype glioblastoma patients, providing a simple stratification method for clinical outcomes (ref: Clavreul doi.org/10.3390/cancers13225778/).