PURPOSE:Differentiating recurrent brain metastases (BM) from treatment-related changes after radiation therapy remains challenging. PURSUE (NCT04410367) evaluated various lesion uptake metrics to establish image interpretation criteria to detect recurrent BM with 18F-fluciclovine positron emission tomography (PET). METHODS AND MATERIALS:Patients with BM were enrolled if they had a previously irradiated MRI-equivocal "reference" lesion and were planned for craniotomy. PET with 18F-fluciclovine (185 MBq) was performed <42 days post-MRI and 1-21 days precraniotomy. Performance of different qualitative thresholds of lesion 18F-fluciclovine uptake on static PET images (10-20 minutes postinjection) versus histopathological standard of truth was assessed by 3 blinded readers, as were semiquantitative (standardized uptake value [SUV]) and dynamic uptake measures, to establish 18F-fluciclovine interpretation criteria. A separate committee reviewed all data to establish interpretation criteria. Following initial review, additional blinded reads were conducted at three timepoints (10-20, 15-25, and 20-30 minutes) to explore visual-only reads (uptake ≥ parotid/pituitary as reference) and SUV ratio (SUVR)-based criteria (SUVpeak(lesion-to-pituitary)). RESULTS:Twenty-three reference lesions from 23 subjects underwent histopathological analysis; 10 (43%) were confirmed as recurrence. At 10-20 minutes postinjection, the highest performing qualitative measure was "uptake higher than parotid" (specificity: 92%-100%; sensitivity: 40%-80% across readers). SUVmax was a high-performing metric on receiver operating characteristic analysis (area under the curve: 0.87, sensitivity: 80%, specificity: 85% for SUVmax threshold = 4.8). Dynamic measures provided no further diagnostic value. Additional reads showed visual-only interpretation was optimal at 15 to 25 minutes (sensitivity: 60%-90%; specificity: 77%-100%). SUVR-based interpretation using a threshold of 1.1 provided 70% to 80% sensitivity and 85% specificity. CONCLUSIONS:PURSUE established effective, histopathologically verified 18F-fluciclovine interpretation criteria for diagnosing recurrent BM after radiation therapy that will help evaluate 18F-fluciclovine PET in future studies.

Abstract Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity and plasticity. GBM tumors contain neoplastic cells within a fluid spectrum of diverse transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we develop scFOCAL (Single-Cell Framework for -Omics Connectivity and Analysis via L1000), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identify compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states, and leverage this capability to predict combination synergy. We validate the significance of these findings in vitro, ex vivo, and in vivo, and use the Olig2 inhibitor CT-179 as a reference drug to identify additional small molecules that would maximize the cell-drug discordance across the GBM transcriptional landscape. Our analysis leads to the combination of Olig2 inhibition with treatment with Depatux-M, of with which we demonstrate synergy in vivo. Our studies suggest that scFOCAL identifies cell states that are sensitive and resistant to targeted therapies in GBM using a measure of cell and drug connectivity, which can be applied to identify new synergistic combinations. Citation Format: Robert K. Suter, Anna M. Jermakowicz, Rithvik Veeramachaneni, Matthew D'Antuono, Longwei Zhang, Rishika Chowdary, Simon Kaeppeli, Madison Sharp, Pravallika Palwai, Vasileios Stathias, Grace Baker, Luz Ruiz, Winston Walters, Maria Cepero, Danielle Burgenske, Edward B. Reilly, Anatol Oleksijew, Mark G. Anderson, Sion Ll. Williams, Michael E. Ivan, Ricardo J. Komotar, Macarena I. De La Fuente, Gregory Stein, Alexandre Wojcinski, Santosh Kesari, Jann N. Sarkaria, Stephan C. Schürer, Nagi G. Ayad. Drug and single-cell gene expression integration identifies heterogeneity-aware synergistic combinations for glioblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr B032.

e14079 Background: Treatment for recurrent GBM is limited and associated with high mortality. We hypothesize that standard of care for GBM induces severe lymphopenia and, by treating lymphopenia both through in-vivo activation of NK & T cells (via NAI subcutaneous injection) and ex-vivo infusion of NK cells (PD-L1 CAR-NK cells), OS can be prolonged. We hypothesize that lymphocytes, responsible for immunogenic cell death and measured by absolute lymphocyte count (ALC), is key to prolonged survival. NAI, an IL-15 receptor agonist, is the first treatment to address lymphopenia by activating and proliferating NK and T-cells. Methods: Phase 2 QUILT-3.078 trial (NCT06061809) of participants with GBM ( IDH WT) who recurred after surgery and temozolomide/XRT. Fourteen participants received PD-L1 t-haNK, an off-the-shelf NK cell therapy with a chimeric antigen receptor (CAR) for PD-L1, NAI and BEV, every two weeks, as outpatients. Five patients also received concurrent tumor treating fields. ALC levels were measured through data cutoff (January 13, 2026). Results: 14 participants have received 139 total doses, with 7/14 (50%) remaining on therapy. One participant had radiographic complete response after four doses. ALC trend increased from baseline and was maintained through cycle 9 among evaluable participants. Median follow-up is 6.75 months (range 2.4-9.3 months) with four deaths on-study, mOS has not been reached. Ten patients had any SAE, of which one was suspected to be related to BEV (pulmonary embolism) and two SAEs were suspected to be related to the experimental therapy (encephalopathy, temporal arteritis). No CRS or ICANS were observed. Conclusions: These findings support that reconstituting lymphocytes (NK & T cells) results in response, including complete response, in recurrent GBM. This is the first report of disease response in participants with recurrent GBM who received orchestrated systemic immunotherapy with CAR-NK cells combined with an IL-15 agonist and BEV. The potential of reversing lymphopenia induced by SOC treatment, prolonging survival, and improving prognosis across tumor types, may be a paradigm change in cancer care. The QUILT-3.078 Phase 2B expansion study is ongoing and a randomized clinical trial in first and second line GBM patients is in development. At the time of submission, 23/34 participants have enrolled on the QUILT-3.078 Phase 2/2B study and updated data will be presented. Clinical trial information: NCT06061809 .

We present the University of California San Diego post-treatment glioblastoma (UCSD-PTGBM) annotated multimodal MRI dataset. The UCSD-PTGBM dataset includes 243 timepoints on 178 subjects with histopathologically-proven glioblastoma who were imaged with an advanced brain tumor protocol on 3 Tesla MRI scanners. Sequences include standard 3D imaging, as well as multishell diffusion (Restricted Spectrum Imaging, RSI) and perfusion imaging techniques (Arterial Spin Labelling, ASL and Dynamic Susceptibility Contrast, DSC), and neuroradiologist approved voxelwise tumor segmentations for both traditional segmentation masks and cellular tumor segmentations. The dataset also includes isocitrate dehydrogenase (IDH) mutation status and O6-methylguianine-DNA methyl-transferase (MGMT) promotor methylation status, as well as overall survival and progression free survival information for a subset of cases. We hope that researchers around the world will use these data to continue to improve analysis of post-operative MRI on glioblastoma patients, translate their findings into clinical practice and improve the management and outcome for these patients.

Pineal parenchymal tumors of intermediate differentiation (PPTID) are aggressive, rare central nervous system tumors. The management of PPTID remains challenging, given the limited number of reported cases and the logistical difficulties in conducting studies on rare tumors such as these. Leptomeningeal disease (LMD) is a relatively frequent pattern of recurrence, and accurate monitoring is essential to optimize potentially efficacious therapies. We present the case of a 27-year-old woman who initially presented with positional headaches and mild blurry vision. Imaging revealed an enhancing third ventricular lesion with obstructive hydrocephalus. She underwent subtotal surgical resection of the tumor and was diagnosed with PPTID. Approximately 14 months later, imaging demonstrated local recurrence with leptomeningeal metastases. In addition to standard therapies, the Biocept IN/CNSide cerebrospinal fluid (CSF) liquid biopsy assay (Biocept, Inc., San Diego, California, US), including tumor cell protein expression biomarkers, ctDNA biomarkers, and tumor cell fluorescence in situ hybridization (FISH) biomarkers, was used to monitor treatment response at seven time points. During this period, CSF cytology and other conventional markers were unremarkable. This case demonstrates how novel CSF-based monitoring technology may improve disease surveillance in patients who develop leptomeningeal disease. Although leptomeningeal metastasis is not uncommon in patients with PPTID, the optimal monitoring approach remains unclear. While this assay remains investigational, it may represent a promising strategy to address an unmet need in the management of PPTID with LMD.

AIM:Chordoma is an ultra-rare malignancy with no approved therapies. In this study, we analyzed individual patient-level data (IPD) for patients with chordoma reconstructed from previously completed clinical trials. Our primary objectives were to synthesize the historical objective response rate (ORR) and to generate a pooled Kaplan-Meier progression-free survival (PFS) curve. Our overarching goal is that these data will inform future trial design and interpretation of results. METHODS:A literature review was conducted to identify prospective chordoma systemic therapy clinical trials. Eligible studies were required to be prospective; to include locally advanced/metastatic conventional chordoma; to report a PFS Kaplan-Meier curve; and to assess PFS/ORR by RECIST (1.0/1.1). IPD were reconstructed from the PFS curves and data were synthesized to estimate the pooled PFS and ORR. RESULTS:Twelve studies met eligibility, contributing 328 patients (320 response evaluable). The combined ORR was 4.7% and median PFS was 10.8 months (95% CI 9, 12). Sensitivity analyses revealed no significant differences in PFS between studies partitioned by study-level variables. In "leave-one-out" analyses of each study alone versus pooled data, only everolimus/imatinib showed a significantly longer PFS (p = 0.0014), with a median PFS of 14.0 months (95% CI 11.5, NA) compared to 10.0 months (95% CI 8.3,11.2) for the remaining pooled cohort (estimated hazard ratio: 0.50 [95% CI 0.33, 0.77]). CONCLUSION:IPD from 12 trials were reconstructed and analyzed, consolidating outcomes for 328 trial-eligible patients with chordoma. The estimated overall response rate (ORR) is 4.7% and median PFS 10.8 months, providing a historical benchmark useful for future trial design. Notably, everolimus/imatinib was the only study treatment associated with a statistically significant improvement in PFS, which may warrant further investigation.

Mesenchymal stromal cells (MSCs) contain several percentages of SSEA-3+ pluripotent-like Muse cells. We compared human bone marrow–derived Muse cells with MSC controls delivered intravenously (IV) or intranasally (IN) in 3 month old 5xFAD mice without immunosuppression. Light sheet imaging of mCherry labeled cells showed markedly greater brain retention of Muse cells at day 7 after IN delivery compared with MSCs. At 16 weeks, human cells, detected by anti–human mitochondria, human nuclear Ku80, and Alu ddPCR, were highly persistent in both Muse groups with neural and microglial marker expression. Muse treatment reduced amyloid β plaque burden and preserved pre-onset Y maze and Morris water maze performance through 16 weeks, with similar outcomes after IV and IN delivery. These findings support further evaluation of IN Muse cell delivery for AD cell therapy.

Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity and plasticity. GBM tumors contain neoplastic cells within a fluid spectrum of diverse transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we develop scFOCAL (Single-Cell Framework for -Omics Connectivity and Analysis via L1000), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identify compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states, and leverage this capability to predict combination synergy. We validate the significance of these findings in vitro, ex vivo, and in vivo, and identify a combination of an OLIG2 inhibitor and Depatux-M for the treatment of GBM. Our studies suggest that scFOCAL identifies cell states that are sensitive and resistant to targeted therapies in GBM using a measure of cell and drug connectivity, which can be applied to identify new synergistic combinations.

Advances in whole-genome sequencing and molecular profiling have led to substantially increased appreciation of the genetic diversity and complexity of brain tumor biology. Through systematic analysis of human tumor samples, neuro-oncology is moving from a histopathological characterization of primary brain tumors to a classification system based on relevant molecular features that more accurately reflect the biological activity of these neoplasms. Specific genetic abnormalities also provide potential therapeutic targets that were previously unidentified, and potentially more effective than the existing therapies. Here, we review the recent developments in the molecular science of adult and pediatric gliomas as well as medulloblastoma.

Genetic and molecular alterations in cancer cells can serve as therapeutic targets and enable more precise, individualized treatment strategies. In rare tumors with limited systemic treatment options, molecular profiling may help identify therapeutic opportunities when conventional approaches are exhausted. We report the case of a 72-year-old woman with a long-standing, multiply recurrent clival chordoma and no remaining surgical or radiation options who experienced a meaningful clinical and metabolic response to targeted therapy. Comprehensive tumor molecular profiling identified an activating isocitrate dehydrogenase 1 (IDH1) p. R132C mutation, which guided off-label treatment with the IDH1 inhibitor ivosidenib. Treatment was well tolerated and associated with durable radiographic response with tumor reduction, partial metabolic response on FDG-PET imaging, and clinically significant improvement in neurological symptoms and quality of life. This case highlights the value of molecular tumor board-guided interpretation of genomic alterations and illustrates the potential role of IDH-targeted therapy in select patients with recurrent chordoma.

BACKGROUND:Immunotherapy has transformed cancer treatment by enhancing cytotoxic T-cell activity and interferon-γ (IFN-γ)-mediated tumor clearance. However, glioblastoma (GBM) remains largely refractory to these approaches, reflecting a profoundly immunosuppressive and myeloid-dominant tumor microenvironment. IFN-γ is central to antitumor immunity, yet chronic exposure can paradoxically promote adaptive resistance. How GBM cells respond to sustained IFN-γ signaling, and whether these responses differ across tumor states, remains poorly understood. METHODS:To address this, we modeled chronic IFN-γ exposure in mesenchymal-like (U87) and proneural-like (U251) GBM cells over 28 days and performed integrated analyses of transcriptional, proteomic, and secretory responses. RESULTS:While IFN-γ initially suppressed growth in both models, their long-term adaptations diverged. U87 cells developed a persistence-prone state characterized by progressive activation of PI3K-AKT signaling, whereas U251 cells exhibited sustained interferon signaling with persistent interferon-related DNA damage resistance signature (IRDS) expression and suppressed AKT activity. These transcriptional and signaling programs were incompletely reversible after cytokine withdrawal, indicating stable interferon conditioning. Analysis of TCGA glioblastoma datasets demonstrated that interferon-associated transcriptional programs are present across human tumors and are positively associated with PI3K-AKT pathway activity across molecular subtypes. CONCLUSIONS:Together, these findings reveal that chronic IFN-γ exposure drives distinct, lineage-dependent adaptive states in GBM, linking interferon signaling to divergent survival and immune-modulatory programs. While IFN-γ enhances immune activation, prolonged signaling may also promote tumor persistence. These results support therapeutic strategies that combine IFN-based approaches with interventions targeting adaptive survival pathways and immune reprogramming.

The poor clinical outcomes of pediatric high-grade glioma (pHGG) highlight the urgent need for new therapies. Oligodendrocyte lineage transcription factor 2 (OLIG2) is a pro-mitotic transcription factor highly expressed in glioma stem cells and may represent a novel therapeutic target. To evaluate the therapeutic efficacy of an OLIG2 inhibitor CT-179 in pHGG, we determined the OLIG2 mRNA expression in 10 patient-derived orthotopic xenograft (PDOX) models. In vitro activities of CT-179 were analyzed in monolayer and neurosphere cells (0-10 µM) with and without radiation (XRT) (0-8 Gy), brain penetration was evaluated in tumor-bearing PDOX mice, and in vivo efficacy was determined at 15-240 mg/kg (oral) alone or combined with XRT (2 Gy/day × 5 days). Changes in animal survival times were analyzed using the Kaplan-Meier method, followed by pair-wise comparisons. Increased OLIG2 mRNA expression was detected in seven out of ten PDOX models. CT-179 inhibited cell viability in a time- and dose-dependent manner in all eight pGBM xenograft tumors (IC50 0.03-10 µM) and was potentiated by XRT (0.03-1 µM). Oral gavage (24 mg/kg) of CT-179 for 5 days led to effective penetration in mouse cerebrum (3232.7 ± 569.2 ng/g), cerebellum (1563.3 ± 269.6 ng/g), brain stem (1685.3 ± 309 ng/g), and PDOX tumors (1814 ± 110.3 ng/g) vs. 361.3 ± 1.5 ng/mL in serum. CT-179 alone was not active at 200 mg/kg in four models, although it was moderately effective at 240 mg/kg in one model. When combined with XRT, a significant extension of animal survival times was observed in two out of four models. Doses needed to eliminate OLIG2 expression in vitro varied from 0.3 to >1 µM in pGBM cells. In summary, our data showed that orally administered CT-179 penetrated the blood-brain barrier (BBB) and exhibited potential for inhibiting pGBM growth when combined with XRT.

Context.— Leptomeningeal disease (LMD) is a clinical sequela of central nervous system metastasis involving the cerebrospinal fluid (CSF), often seen in late-stage solid tumors. It has a grave prognosis without urgent treatment. Standard of care methodologies to diagnose LMD include CSF cytology, magnetic resonance imaging, and clinical evaluation. These methods offer limited sensitivity and specificity for the evaluation of LMD. Here, we describe the analytic performance characteristics of a microfluidic-based tumor cell enrichment and detection assay optimized to detect epithelial cells in CSF using both contrived samples as well as CSF from patients having suspected or confirmed LMD from carcinomas. Objective.— To demonstrate the feasibility of using a microfluidic, multi-antibody cell capture assay to identify and quantify tumor cells in CSF. Design.— An artificial CSF solution was spiked with 34 different human carcinoma cell lines at different concentrations and assayed for the ability to detect tumor cells to assess analytic accuracy. Two cell lines were selected to assess linearity, intra-assay precision, interinstrument precision, and sample stability. Clinical verification was performed on 65 CSF specimens from patients. Parameters assessed included the number of tumor cells, coefficient of variation percentage, and percentage of tumor cell capture (TCC). Results.— Among contrived samples, average tumor cell capture ranged from 50% to 82% (261 of 522; 436 of 531), and coefficients of variation ranged from 7% to 67%. The cell capture assay demonstrated a sensitivity of 92% and a specificity of 95% among clinical samples. Conclusions.— This assay demonstrated the ability to detect and enumerate epithelial cells in contrived and clinical specimens in an accurate and reproducible fashion. The use of cell capture assays in CSF may be useful as a sensitive test for the diagnosis and longitudinal monitoring of LMD from solid tumors.

Brain accumulation of amyloid-ß 1-42 (Aß) in plaques and neurons is the cause of AD neuropathology that is opposed by autologous monocyte/macrophages (MMs) in health but this defense fails in AD. RNAseq, immunochemistry of the brain, immunofluorescence, and confocal microscopy of macrophages. In the AD brain, MMs shuttle Aß from parenchyma to vessels, which develop vasculitis, causing amyloid-related imaging abnormalities (ARIAs). AD patients’ MMs are inflammatory and lack enzymes in energy, and chaperones for unfolded protein response (UPR) and Aß degradation. Epoxides of polyunsaturated fatty acids (EpFAs), in combination with the inhibitors of soluble epoxide hydrolase (sEH) TPPU or EC5026 or the cGAS/STING pathway, regulate in macrophages in a homeostatic fashion Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) transcripts, and recover a pro-resolution macrophage phenotype. The repaired macrophages display increased phagocytosis of FITC- Aß at 2 hours and increased degradation of Aβ at 24 hours. Others showed in a mouse model that restoration of cellular bioenergetics through inhibition of the prostaglandin E2 (PGE2) receptor 4 (EP4R) signaling restored cognition. Inhibiting macrophage inflammation by the sEH receptor inhibitors TPPU and EC5026 or the STING inhibitor H-151 in AD macrophages could restore cognition in AD patients.

PURPOSEAccurate human leukocyte antigen (HLA) typing is an essential step for designing peptide vaccines used in the personalized neoantigen peptide vaccine immunotherapy (PNPVT) in patients with cancer. The reasons for variation in the patient response to PNPVT are yet unknown. One of the reasons could be the somatic changes in the HLA genes in the cancer cells. The objective of the present research was to analyze the somatic status of HLA class I genes in cancer tissue through integrative genomic analysis and to identify high-confidence subset of potentially functional cancer somatic HLA class I genotype relevant to PNPVT.PATIENTS AND METHODSWhole-exome (paired tumor-normal) and RNAseq (tumor) paired-end sequencing data from 24 patients with cancer were used for the analysis. The genotyping of HLA class I was performed using four HLA typing software tools. To assess the functional status of HLA class I genes in the cancer tissue, we analyzed somatic mutation, HLA gene loss of heterozygosity, and chromosome 6 copy loss status in cancer exome data.RESULTSSomatic mutations in HLA genes were detected in the tumor data of five patients, and somatic HLA gene loss of heterozygosity was identified in the tumor data of five patients. Complete or partial chromosome 6 copy loss was detected in eight patient samples.CONCLUSIONThe results indicate that HLA class I genes may get affected by somatic changes in cancer tissue, and assessment of the somatic status of the HLA genotype should be performed in the cancer tissues. The results provide robust rational for removal of mutated or lost HLAs from the personalized neoantigen peptide prediction pipeline to potentially increase the efficacy of the PNPVT. Further functional studies are needed to assess the impact of HLA gene mutations/loss on PNPVT outcomes.

Glioblastoma (GBM) is a lethal brain cancer with no effective treatment; understanding how GBM cells respond to tumor microenvironment remains challenging as conventional cell cultures lack proper cytoarchitecture while in vivo animal models present complexity all at once. Developing a culture system to bridge the gap is thus crucial. Here, a multicellular approach is employed using human glia and vascular cells to optimize a 3D brain vascular niche model that enabled not only long-term culture of patient derived GBM cells but also recapitulation of key features of GBM heterogeneity, in particular invasion behavior and vascular association. Comparative transcriptomics of identical patient derived GBM cells in 3D and in vivo xenotransplants models revealed that glia-vascular contact induced genes concerning neural/glia development, synaptic regulation, as well as immune suppression. This gene signature displayed region specific enrichment in the leading edge and microvascular proliferation zones in human GBM and predicted poor prognosis. Gene variance analysis also uncovered histone demethylation and xylosyltransferase activity as main themes for gene adaption of GBM cells in vivo. Furthermore, the 3D model also demonstrated the capacity to provide a quiescence and a protective niche against chemotherapy.

Diagnostic practices for schizophrenia are unreliable due to the lack of a stable biomarker. However, machine learning holds promise in aiding in the diagnosis of schizophrenia and other neurological disorders. Dysregulated miRNAs were extracted from public sources. Datasets of miRNAs selected from the literature and random miRNAs with designated gene targets along with related pathways were assigned as descriptors of machine-learning models. These data were preprocessed and classified using WEKA and TensorFlow, and several classifiers were tested to train the model. The Sequential neural network developed by authors performed the best of the classifiers tested, achieving an accuracy of 94.32%. Naïve Bayes was the next best model, with an accuracy of 72.23%. MLP achieved an accuracy of 65.91%, followed by Hoeffding tree with an accuracy of 64.77%, Random tree with an accuracy of 63.64%, Random forest, which achieved an accuracy of 61.36%, and lastly ADABoostM1, which achieved an accuracy of 53.41%. The Sequential neural network and Naïve Bayes classifier were tested to validate the model as they achieved the highest accuracy. Naïve Bayes achieved a validation accuracy of 72.22%, whereas the sequential neural network achieved an accuracy of 88.88%. Our results demonstrate the practicality of machine learning in psychiatric diagnosis. Dysregulated miRNA combined with machine learning can serve as a diagnostic aid to physicians for schizophrenia and potentially other neurological disorders as well.

Glioblastoma (GBM) represents one of the most aggressive brain tumors with a poor prognosis despite decades of research. Epigenetic regulation has emerged as a promising strategy for managing aggressive cancers, such as GBM, by modulating pro-tumorigenic gene expression. The role of pro-tumorigenic genes, such as oligodendrocyte transcription factor 2 (OLIG2), has been heavily associated with cancer progression and treatment resistance and is a potential target for GBM. The objective of this study is to analyze the effectiveness of various epigenetic regulators, including histone modifiers, DNA methylases, chromatin remodelers, and miRNAs, on OLIG2 expression, including the effectiveness of individual epigenetic regulators and their combinations. The effects of epigenetic regulators in GBM that are found in the literature were reviewed for their survival and co-expression with OLIG2. We found that KDM6B, BRG1, DNMT1, and HDAC2 were associated with significant co-expression with OLIG2 and decreased survival in GBM patients, reinforcing their suitability as targets. Additionally, miR-17-3p miRNAs associated with silencing OLIG2 as gene expression was downregulated in GBM. Additionally, this paper highlights the potential of combination therapies targeting multiple epigenetic pathways simultaneously. A kinase inhibitor (alisertib), together with JQ1, reduced the tumor growth of GBM cells in vivo more than either treatment alone, making combination therapies a promising solution.

Background The complexities of the field of neuro-oncology require multidisciplinary collaboration in order to deliver contemporary comprehensive care. There is increasing awareness that much of neuro-oncology care occurs in the community setting. In 2022, the Society for Neuro-Oncology (SNO) created the Community Neuro-Oncology Committee (CNO) in an inaugural attempt to formally acknowledge community neuro-oncology practitioners. Methods A 19 question survey was developed by SNO-CNO to gather initial data on the current landscape of neuro-oncology care in the community. The survey was distributed via the SNO newsletter and email blasts as well as through partnerships with multiple advocacy groups. Results were analyzed and tabulated through R2. Results There were 112 responses from providers in the United States and Canada. Most providers were physicians and represented multiple disciplines including neurology, neuro-oncology, medical oncology, neurosurgery, and radiation oncology. Sixty-four (57%) described themselves as neuro-oncology-focused. Eighty-eight (79%) reported access to neuro-oncology tumor boards. Sixty-eight (73%) stated they had access to molecular tumor boards. Most respondents felt that they were adequately supported to manage neuro-oncology patients. When dividing responses based on a neuro-oncology-focused practice compared to a less neuro-oncology-focused practice, there were significant differences between access to molecular tumors boards (85% vs 63%, P = .023) and access to clinical trials (98% vs 82%, P = .022). Conclusion This qualitative and quantitative hypothesis-generating data is the start of understanding the challenges faced by community neuro-oncology providers. These results will guide future studies and recommendations aimed toward better supporting them and their patients.