In addition to immune evasion, GBM's resistance to therapies is compounded by its intricate TME. A novel self-homing liposomal nanobot was developed to navigate the blood-brain barrier (BBB) and deliver chemotherapy directly to the tumor, utilizing the acidic and glucose-rich environment of the TME for targeted drug release (ref: Cheng doi.org/10.1002/anie.202512948/). This approach aims to overcome the challenges posed by the BBB and TME, which often limit the effectiveness of conventional treatments. Moreover, targeting the CHK2-YBX1&YBX3 hub has been proposed as a strategy to enhance immune checkpoint blockade responses, highlighting the potential for combining therapies to improve patient outcomes (ref: Ali doi.org/10.1093/neuonc/). The exploration of ENPP1 as an innate immune checkpoint also presents a promising avenue for enhancing therapeutic responses, particularly in patients who do not respond to traditional immune checkpoint inhibitors (ref: Wang doi.org/10.1016/j.xcrm.2025.102336/). Overall, these findings emphasize the necessity of understanding and manipulating the TME to develop effective therapeutic strategies for GBM.

Moreover, the reciprocal regulation of EGFR and ZBED1 has been implicated in promoting stemness and tumorigenesis in GBM, highlighting the complex interplay between genetic factors and tumor behavior (ref: Hou doi.org/10.1093/neuonc/). The use of TurboID for profiling extracellular vesicle cargo proteins has provided insights into the molecular composition of GBM, which may inform future therapeutic strategies (ref: Russo doi.org/10.1002/jev2.70158/). Tumor heterogeneity, particularly in NF1-mutant GBM, has been shown to influence clinical outcomes and responses to MEK inhibitors, underscoring the need for personalized treatment approaches based on genetic profiling (ref: Pan doi.org/10.1172/jci.insight.192658/). Lastly, CDK12's role in regulating cellular metabolism presents a potential target for therapy, as its inhibition has been associated with significant survival benefits in preclinical models (ref: Mun doi.org/10.1172/jci.insight.190780/). Collectively, these studies illustrate the intricate molecular mechanisms underlying GBM and the potential for targeted therapies that address specific genetic vulnerabilities.

The development of biomimetic nanoplatforms for multimodal therapy also represents a significant advancement in GBM treatment. A platinum-based nanoplatform has been designed to enhance chemodynamic therapy and photothermal conversion, addressing the challenges posed by the TME and BBB (ref: Chen doi.org/10.1016/j.jcis.2025.139082/). Furthermore, hydrogen sulfide therapy has shown promise in inhibiting the recruitment of tumor-associated macrophages, which could improve survival outcomes in IDH-wildtype GBM (ref: Camarano doi.org/10.1016/j.redox.2025.103866/). These findings highlight the importance of exploring novel therapeutic strategies that target the unique characteristics of GBM, particularly in the context of treatment resistance and the immunosuppressive TME.

Moreover, the generation of orthotopic intracranial patient-derived xenograft models has provided valuable insights into the molecular features of GBM and potential therapeutic responses, facilitating the evaluation of new treatment modalities (ref: Tran doi.org/10.1016/j.neo.2025.101233/). The exploration of histone deacetylase 7 (HDAC7) in GBM has revealed its role in reprogramming the chromatin landscape, which may influence treatment responses and tumor progression (ref: Hassan doi.org/10.1016/j.jbc.2025.110732/). Collectively, these studies underscore the critical role of surgical and treatment approaches in managing GBM, emphasizing the need for ongoing research to refine strategies that enhance patient survival and quality of life.

The use of TurboID for profiling extracellular vesicle cargo proteins has provided insights into the molecular composition of GBM, which may inform future therapeutic strategies (ref: Russo doi.org/10.1002/jev2.70158/). Furthermore, the interplay between stemness and tumorigenesis has been explored, with findings suggesting that targeting specific pathways may enhance treatment efficacy in heterogeneous tumor populations (ref: Hou doi.org/10.1093/neuonc/). These studies collectively emphasize the importance of understanding stem cell dynamics and tumor heterogeneity in developing effective therapeutic strategies for GBM.

Additionally, a biomimetic platinum-based nanoplatform has been designed to improve multimodal therapy for GBM, combining chemodynamic therapy with photothermal conversion to enhance treatment outcomes (ref: Chen doi.org/10.1016/j.jcis.2025.139082/). The generation of orthotopic intracranial patient-derived xenograft models has also facilitated the evaluation of new therapeutic approaches, allowing for a better understanding of drug delivery dynamics in a more clinically relevant context (ref: Tran doi.org/10.1016/j.neo.2025.101233/). These advancements in drug delivery systems highlight the ongoing efforts to improve therapeutic efficacy and patient outcomes in the face of GBM's inherent challenges.

Moreover, the exploration of novel therapeutic agents, such as the thioredoxin reductase 1 inhibitor BS1801, has shown promise in relieving treatment resistance and inducing apoptosis in GBM cells (ref: Chang doi.org/10.1016/j.redox.2025.103827/). Additionally, hydrogen sulfide therapy has demonstrated potential in improving survival outcomes by inhibiting the recruitment of tumor-associated macrophages, further emphasizing the importance of understanding the tumor microenvironment in shaping clinical outcomes (ref: Camarano doi.org/10.1016/j.redox.2025.103866/). Collectively, these findings underscore the need for ongoing research to identify prognostic factors and develop targeted therapies that can improve survival rates in GBM patients.

Additionally, the integration of molecular diagnostics into clinical practice has been emphasized in the latest WHO classification of CNS tumors, which aims to refine tumor classification and inform treatment strategies based on genetic profiles (ref: Bernstock doi.org/10.1038/s41591-025-03952-9/). The ongoing exploration of biomarkers related to treatment resistance and tumor progression will be essential for developing personalized therapies that address the unique characteristics of each patient's tumor. These advancements in biomarkers and diagnostics are pivotal for enhancing the precision of GBM treatment and improving overall patient care.