Tumor heterogeneity is a significant challenge in understanding glioblastomas (GBMs), which are characterized by extensive inter- and intratumor variability. Recent studies have utilized patient-derived models, such as organoids and explants, to investigate this heterogeneity. For instance, LeBlanc et al. analyzed genomic features across 12 IDH wild-type GBMs and found that patient-derived explants and gliomasphere lines retained variable genomic characteristics, highlighting the complexity of GBM heterogeneity (ref: LeBlanc doi.org/10.1016/j.ccell.2022.02.016/). Furthermore, Wang et al. characterized distinct circular RNA signatures across various solid tumors, including GBM, revealing that these RNA molecules could play a role in tumor initiation and progression (ref: Wang doi.org/10.1186/s12943-022-01546-4/). Miki et al. focused on the TERT promoter C228T mutation, which is prevalent in GBM and confers a growth advantage in neural progenitors, suggesting that this mutation is an early event in gliomagenesis (ref: Miki doi.org/10.1093/neuonc/). Additionally, Mladek et al. explored the RBBP4-p300 axis, which modulates essential survival genes in GBM, proposing it as a potential therapeutic target (ref: Mladek doi.org/10.1093/neuonc/). Jiang et al. provided insights into metabolic adaptations in GBM, demonstrating that fatty acid oxidation contributes to radioresistance and immune evasion, particularly through the CD47 pathway (ref: Jiang doi.org/10.1038/s41467-022-29137-3/). Binder et al. summarized the current state of GBM biology and therapeutic strategies, emphasizing the need for innovative approaches to achieve durable remissions (ref: Binder doi.org/10.1158/0008-5472.CAN-21-3534/).

The therapeutic landscape for glioblastoma (GBM) is evolving, with new strategies aimed at overcoming drug resistance and improving patient outcomes. Wang et al. developed M1 macrophage-derived extracellular vesicles (M1EVs) that effectively target GBM, demonstrating strong synergistic therapeutic effects (ref: Wang doi.org/10.1038/s41392-022-00894-3/). Zhan et al. introduced a blood exosome-based delivery system for cPLA2 siRNA and metformin, targeting GBM energy metabolism to enhance therapeutic efficacy (ref: Zhan doi.org/10.1093/neuonc/). Le Rhun et al. investigated the prognostic significance of therapy-induced myelosuppression, finding that lower baseline neutrophil counts correlate with better progression-free survival (PFS) and overall survival (OS) in newly diagnosed GBM patients (ref: Le Rhun doi.org/10.1093/neuonc/). Moujalled et al. demonstrated that BH3 mimetic drugs enhance the efficacy of Temozolomide and JQ1 in GBM cell lines, indicating a potential combinatorial approach to treatment (ref: Moujalled doi.org/10.1038/s41418-022-00977-2/). Ali et al. highlighted the role of myeloperoxidase in the glioma microenvironment post-radiotherapy, suggesting its potential as a therapeutic target (ref: Ali doi.org/10.1016/j.neo.2022.100779/). Kim et al. isolated two distinct cancer cell lines from the same GBM tissue, revealing intratumoral heterogeneity that could inform therapeutic strategies (ref: Kim doi.org/10.1007/s00018-022-04188-3/). Cameron et al. validated a spectroscopic liquid biopsy for earlier brain cancer detection, which could significantly impact treatment timelines (ref: Cameron doi.org/10.1093/noajnl/).

Understanding the molecular mechanisms underlying glioblastoma (GBM) is crucial for developing targeted therapies. Chen et al. identified FOSL1 as a key regulator of the proneural-to-mesenchymal transition in GBM stem cells, linking its expression to tumor-initiating capabilities (ref: Chen doi.org/10.1016/j.ymthe.2021.10.028/). Kwak et al. demonstrated that HDAC2 knockdown inhibits GLUT3, leading to reduced tumorigenesis through altered glucose metabolism, highlighting the role of epigenetic regulation in GBM (ref: Kwak doi.org/10.1186/s13046-022-02305-5/). Liu et al. provided insights into chromosomal instability in IDH-mutant astrocytomas, emphasizing the need to integrate this molecular feature into tumor classification (ref: Liu doi.org/10.1186/s40478-022-01339-2/). Ryskalin et al. explored the relationship between mTOR activity and alpha-synuclein accumulation in GBM cells, suggesting that autophagy modulation could influence tumor behavior (ref: Ryskalin doi.org/10.3390/cancers14061382/). Yang et al. characterized slow-cycling cells within GBM, which exhibit properties of cancer stem cells and contribute to treatment resistance (ref: Yang doi.org/10.3390/cancers14051126/).

The immune microenvironment plays a pivotal role in glioblastoma (GBM) progression and response to therapy. Najem et al. conducted a comprehensive analysis of immune cell profiles in gliomas and lung metastases, revealing distinct immune cell localization patterns that could inform immunotherapeutic strategies (ref: Najem doi.org/10.1172/jci.insight.157612/). Wang et al. highlighted the role of EWI2 in suppressing glioblastoma and other cancers, suggesting its potential as a therapeutic target (ref: Wang doi.org/10.1016/j.canlet.2022.215641/). Perlow et al. pooled data from multiple trials to assess accelerated hypofractionated radiation for elderly or frail GBM patients, providing evidence for alternative treatment regimens that may improve outcomes (ref: Perlow doi.org/10.1002/cncr.34192/). Liu et al. proposed RAGE inhibitors as alternatives to dexamethasone for managing cerebral edema post-surgery, aiming to reduce complications associated with corticosteroid use (ref: Liu doi.org/10.1007/s13311-022-01207-w/). Chen et al. demonstrated that TSSC4 overexpression can prevent TMZ-induced autophagy and cell death in GBM cells, indicating a potential avenue for enhancing therapeutic efficacy (ref: Chen doi.org/10.3389/fcell.2022.823251/).

Metabolic reprogramming is a critical aspect of glioblastoma (GBM) biology, influencing tumor growth and treatment resistance. Cheng et al. utilized VCAM-1-targeted MRI to improve detection of the tumor-brain interface, revealing insights into the metabolic environment of GBM (ref: Cheng doi.org/10.1158/1078-0432.CCR-21-4011/). Tsai et al. investigated the role of Sp1 in temozolomide resistance, finding that metabolic alterations associated with arachidonate metabolism enhance mitochondrial activity in resistant GBM cells (ref: Tsai doi.org/10.1186/s12929-022-00804-3/). Ji et al. introduced a novel PI3K inhibitor, XH30, which effectively suppressed GBM growth in both subcutaneous and orthotopic models, highlighting the importance of targeting metabolic pathways (ref: Ji doi.org/10.1016/j.apsb.2021.05.019/). Le Bras et al. emphasized the role of RNA-binding proteins in translational regulation, which is crucial for GBM proliferation and survival (ref: Le Bras doi.org/10.3390/cancers14051283/). Wurtemberger et al. examined diffusion microstructure imaging to differentiate GBM from brain metastases, suggesting that metabolic profiling could aid in diagnosis (ref: Wurtemberger doi.org/10.3390/cancers14051155/).

The identification of diagnostic and prognostic biomarkers is essential for improving glioblastoma (GBM) management. Liu et al. applied mid-infrared imaging with heavy water labeling to map metabolic tissue profiles, which could enhance our understanding of GBM pathology (ref: Liu doi.org/10.1002/advs.202105437/). Perini et al. utilized high-throughput analysis of 3D cancer models to assess the effects of graphene quantum dots on GBM, providing insights into potential therapeutic applications (ref: Perini doi.org/10.3390/ijms23063217/). Ning et al. explored the role of GBAS in ovarian cancer, demonstrating its impact on cell proliferation and migration, which may have implications for GBM as well (ref: Ning doi.org/10.1093/oncolo/). Ryskalin et al. investigated the spreading of alpha-synuclein from GBM cells to astrocytes, correlating this with stem-like properties, which could serve as a biomarker for tumor aggressiveness (ref: Ryskalin doi.org/10.3390/cancers14061417/). Lee et al. examined the role of XAF1 in GBM response to temozolomide, suggesting its potential as a prognostic biomarker (ref: Lee doi.org/10.1093/noajnl/).

Innovative therapeutic approaches and technologies are crucial for advancing glioblastoma (GBM) treatment. Binder et al. reviewed the current state of GBM biology and therapeutic strategies, advocating for adaptive clinical trial designs to expedite the translation of novel therapies (ref: Binder doi.org/10.1158/0008-5472.CAN-21-3534/). Khan et al. characterized an injectable thiol-Michael addition hydrogel designed for compatibility with GBM therapy, aiming to mitigate tumor recurrence post-surgery (ref: Khan doi.org/10.1016/j.actbio.2022.03.016/). Raevskiy et al. demonstrated better agreement between transcriptomic and proteomic data at the molecular pathway activation level, suggesting that pathway-level analysis could enhance therapeutic targeting (ref: Raevskiy doi.org/10.3390/ijms23052611/). Struve et al. highlighted increased replication stress and R-loop accumulation in EGFRvIII-expressing GBM, presenting new therapeutic opportunities (ref: Struve doi.org/10.1093/noajnl/). Yang et al. identified slow-cycling cells in GBM that contribute to treatment resistance, emphasizing the need for therapies targeting these specific populations (ref: Yang doi.org/10.3390/cancers14051126/).