Glioblastomas (GBMs) are characterized by significant inter- and intratumor heterogeneity, which complicates treatment strategies. Recent studies have utilized patient-derived models, such as organoids and explants, to better understand this heterogeneity. For instance, LeBlanc et al. analyzed genomic features across 12 IDH wild-type GBMs, revealing variable retention of heterogeneity in patient-derived explants and gliomasphere lines (ref: LeBlanc doi.org/10.1016/j.ccell.2022.02.016/). Furthermore, Jiang et al. demonstrated that enhanced mitochondrial fatty acid oxidation (FAO) is linked to radioresistance in GBM, with CD47-mediated immune evasion being a critical factor in recurrent cases (ref: Jiang doi.org/10.1038/s41467-022-29137-3/). This metabolic shift from glycolysis to FAO was shown to correlate with poor prognosis in patients, highlighting the need for targeted therapies that address these metabolic pathways. Additionally, Miki et al. identified TERT promoter mutations as early events in gliomagenesis, suggesting that these mutations confer a growth advantage in neural progenitors (ref: Miki doi.org/10.1093/neuonc/). The integration of these findings emphasizes the importance of understanding the molecular underpinnings of GBM to develop effective treatments. Moreover, Zhan et al. proposed a novel approach for personalized therapy by targeting glioblastoma energy metabolism through blood exosome-based delivery systems (ref: Zhan doi.org/10.1093/neuonc/). This innovative strategy aims to enhance therapeutic efficacy while minimizing systemic side effects.

The molecular landscape of brain tumors is complex, with various genetic and epigenetic factors influencing tumor behavior and treatment response. Mohamed et al. explored the PI3K/AKT/mTOR signaling pathway in IDH-mutant diffuse gliomas, revealing its role in disease progression and potential as a therapeutic target (ref: Mohamed doi.org/10.1093/neuonc/). This pathway's activity was found to be heterogeneous, necessitating robust assessment methods for clinical samples. In a different context, Wang et al. identified elevated Kir2.1 and nuclear N2ICD as markers of a highly malignant subtype of non-WNT/SHH medulloblastomas, underscoring the need for targeted therapies in these challenging cases (ref: Wang doi.org/10.1038/s41392-022-00890-7/). Additionally, the study by Najem et al. highlighted the immune interactome's role in CNS tumors, demonstrating that immune cell localization varies significantly between primary gliomas and metastatic tumors, which could inform immunotherapeutic strategies (ref: Najem doi.org/10.1172/jci.insight.157612/). The interplay between tumor genetics and the immune microenvironment is crucial for understanding tumor progression and developing effective therapies.

Neuroinflammation plays a pivotal role in the progression and treatment response of CNS tumors. Zhou et al. investigated the meningeal lymphatic system's influence on radiotherapy efficacy, demonstrating that the MLV-CLN network enhances anti-tumor immunity and contributes to improved treatment outcomes (ref: Zhou doi.org/10.1038/s41422-022-00639-5/). This finding suggests that targeting lymphatic pathways could augment the effectiveness of existing therapies. In parallel, Jiang et al. reported that fatty acid oxidation fuels glioblastoma radioresistance, with CD47-mediated immune evasion being a significant factor in recurrent GBM (ref: Jiang doi.org/10.1038/s41467-022-29137-3/). These studies collectively emphasize the importance of understanding the immune landscape in CNS tumors, as it directly impacts therapeutic strategies. Furthermore, the research by Fu et al. on racial disparities in COVID-19 outcomes among cancer patients highlights the need for tailored approaches that consider demographic factors in treatment planning (ref: Fu doi.org/10.1001/jamanetworkopen.2022.4304/). The intersection of neuroinflammation, immune response, and patient demographics presents a multifaceted challenge in optimizing care for CNS tumor patients.

Clinical outcomes in brain tumor patients are influenced by various prognostic factors, including treatment-related myelosuppression and genetic alterations. Le Rhun et al. found that lower baseline neutrophil counts correlate with better progression-free survival (PFS) and overall survival (OS) in newly diagnosed glioblastoma patients undergoing temozolomide chemoradiotherapy (ref: Le Rhun doi.org/10.1093/neuonc/). This suggests that myelosuppression may serve as a prognostic indicator, warranting further investigation. Additionally, Lassman et al. conducted a phase II study on infigratinib, a selective FGFR inhibitor, in patients with recurrent gliomas harboring FGFR alterations, demonstrating its potential as a targeted therapy (ref: Lassman doi.org/10.1158/1078-0432.CCR-21-2664/). The findings from these studies underscore the importance of identifying and validating prognostic factors to enhance patient stratification and treatment outcomes. Furthermore, Ferraro et al. examined the incidence of brain metastases in HER2-positive breast cancer patients, revealing no significant differences in metastasis rates based on pathological complete response status, which challenges existing assumptions about treatment efficacy (ref: Ferraro doi.org/10.1038/s41523-022-00380-7/). These insights into clinical outcomes and prognostic factors are critical for improving therapeutic strategies in brain tumor management.

Innovative therapeutic strategies are crucial for improving outcomes in brain tumor patients, particularly given the challenges posed by the blood-brain barrier and tumor heterogeneity. Wang et al. developed a lipoprotein-biomimetic nanostructure designed for targeted delivery of therapeutics to gliomas, enhancing the efficacy of photo-gene therapy while minimizing damage to surrounding healthy tissue (ref: Wang doi.org/10.1016/j.bioactmat.2021.10.039/). This approach leverages the natural properties of high-density lipoproteins to facilitate tumor penetration. Additionally, Sasame et al. explored HSP90 inhibition as a means to overcome resistance to molecular targeted therapy in BRAFV600E-mutant high-grade gliomas, demonstrating potent cytotoxic effects in resistant models (ref: Sasame doi.org/10.1158/1078-0432.CCR-21-3622/). These findings highlight the potential of targeting specific molecular pathways to enhance therapeutic efficacy. Furthermore, Qin et al. emphasized the importance of addressing intratumoral heterogeneity in medulloblastomas, proposing that targeting the secretome may disrupt interclonal communication and tumor progression (ref: Qin doi.org/10.1093/neuonc/). Collectively, these innovative approaches underscore the need for continued research into novel therapeutic strategies that can effectively address the complexities of brain tumors.

The identification of reliable biomarkers and diagnostic techniques is essential for advancing neuro-oncology. Vaz-Luis et al. conducted a longitudinal analysis of fatigue trajectories in breast cancer survivors, highlighting the need for comprehensive assessments of patient-reported outcomes in cancer care (ref: Vaz-Luis doi.org/10.1200/JCO.21.01958/). This study underscores the importance of integrating patient-reported data into clinical practice to better understand treatment impacts. Additionally, the research by van der Spek et al. on inherited variants in CHD3 illustrates the challenges of diagnosing neurodevelopmental disorders, emphasizing the need for improved genetic screening strategies (ref: van der Spek doi.org/10.1016/j.gim.2022.02.014/). Furthermore, Huang et al. investigated the role of long noncoding RNAs in regulating ferroptosis in gastric cancer, suggesting potential biomarkers for tumor behavior and treatment response (ref: Huang doi.org/10.7150/ijbs.69454/). These studies collectively highlight the critical role of biomarkers and diagnostic techniques in enhancing our understanding of brain tumors and improving patient outcomes.

Genetic and epigenetic factors significantly influence the development and progression of brain tumors. Miki et al. focused on TERT promoter mutations, which are prevalent in glioblastomas and are among the earliest events in gliomagenesis, conferring a growth advantage to neural progenitors (ref: Miki doi.org/10.1093/neuonc/). This highlights the importance of understanding genetic alterations in the context of tumor biology. Additionally, Lassman et al. conducted a study on FGFR alterations in recurrent gliomas, demonstrating the potential of targeted therapies to improve outcomes for patients with specific genetic profiles (ref: Lassman doi.org/10.1158/1078-0432.CCR-21-2664/). Moreover, Wang et al. identified a malignant subtype of medulloblastomas characterized by elevated Kir2.1 and nuclear N2ICD, emphasizing the need for targeted approaches in these challenging cases (ref: Wang doi.org/10.1038/s41392-022-00890-7/). The interplay between genetic mutations and epigenetic modifications presents a complex landscape that requires further exploration to develop effective therapeutic strategies.