Brain Tumor Research News & Updates

Research Progress


Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity

January 10, 2022

Nature Communications [free full-text/open-access]

Using machine learning, the authors of this paper overlayed concordant transcriptional information from glioblastoma samples and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. They also highlight differential drug sensitivities and relative chemoresistance in glioblastoma cell lines with enhanced KRAS programs. These pharmacological differences are less pronounced in transcriptional glioblastoma subgroups suggesting that this model may provide insights for targeting heterogeneity and overcoming therapy resistance.

Phase I study of high-dose L-methylfolate in combination with temozolomide and bevacizumab in recurrent IDH wild-type high-grade glioma 

January 5, 2022

Cancer Research Communications [free full-text/open-access]

In this early phase, small trial researchers show that the DNA methylome can be modified in GBM with L-methylfolate (LMF) treatment and that this approach might be useful in methylome priming prior to immunotherapy.


Widely-available drug may benefit glioblastoma treatment

December 17, 2021

NBTS Blog [free article]

Based on data from NBTS’s Defeat GBM Research Collaborative and with support from the Sharpe family, Dr. Paul Mischel (Stanford University) and his laboratory team found that the antidepressant drug, fluoxetine (common brand name: Prozac), potently targets tumor metabolism and inhibits epidermal growth factor (EGFR) signaling, triggering the killing of glioblastoma (GBM) cells. Dr. Mischel’s research also found that “combining fluoxetine with temozolomide, a standard of care for GBM, causes massive increases in GBM cell death and complete tumor regression in mice.” These findings call for a prospective human clinical trial to be conducted, the results of which may lead to adding fluoxetine to standard treatment. 

Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly diagnosed glioblastoma: A phase I study

December 15, 2021

Nature Scientific Reports [free full-text/open-access]

This phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in adult Asian patients with newly diagnosed glioblastoma. In this small trial, adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy. Further trials are needed to confirm these results.

Targeting radiation-tolerant persister cells as a strategy for inhibiting radioresistance and recurrence in glioblastoma 

December 14, 2021

Neuro-Oncology [free full-text/open-access]

This paper’s authors suggest that the NF-κB–YY1–miR-103a regulatory axis is indispensable for the function of RTP cells in driving radioresistance and recurrence and that their results identified a novel strategy for improving survival in patients with recurrent/refractory GBM.

Revised clinical and molecular risk strata define the incidence and pattern of failure in medulloblastoma following risk-adapted radiotherapy and dose-intensive chemotherapy: results from a phase III multi-institutional study

December 11, 2021

Neuro-Oncology [free abstract, subscription required for full article]

The authors of this paper characterized the patterns of progression across medulloblastoma (MB) clinical risk and molecular subgroups from SJMB03, a phase III clinical trial, and suggest that the distinct anatomic failure patterns found across MB subgroups necessitate the consideration of subgroup-specific treatment strategies for these patients.

Tumor mutation burden, expressed neoantigens, and the immune microenvironment in diffuse gliomas

December 3, 2021

Cancers [free full-text/open-access]

The goal of this study was to systematically investigate the association between tumor mutational burden (TMB), expressed neoantigens, and the tumor immune microenvironment in IDH-mutant and IDH-wildtype gliomas. The authors demonstrated that TMB positively correlated with expressed neoantigens, but inversely correlated with immune score in IDH-wildtype tumors but showed no correlation in IDH-mutant tumors. The antigen processing and presenting (APP) score may have potential as a clinical biomarker to predict immune therapy response in gliomas. Lastly, 19% of patients had pathogenic or likely pathogenic germline mutations, primarily in DNA damage repair genes.

Human endogenous retrovirus type K promotes proliferation and confers sensitivity to anti-retroviral drugs in Merlin-negative schwannoma and meningioma

December 1, 2021

Cancer Research [free abstract, subscription required for full article]

In this study, researchers show that FDA-approved retroviral protease inhibitors ritonavir, atazanavir, and lopinavir reduced proliferation of schwannoma and grade I meningioma cells. These results identify HERV-K as a critical regulator of progression in Merlin-deficient tumors and offer potential strategies for therapeutic intervention.

Adenosine A2A receptor activation enhances blood-tumor barrier permeability in a rodent glioma model 

December 1, 2021

Molecular Cancer Research [free full-text/open-access]

This study provides insight on the use of a vasoactive agent to increase exposure of the brain-tumor barrier to chemotherapy with an intention to improve glioma treatment efficacy.

Tumor cell IDO enhances immune suppression and decreases survival independent of tryptophan metabolism in glioblastoma

December 1, 2021

Clinical Cancer Research [free full-text/open-access]

This laboratory study reveals a nonmetabolic tryptophan (Trp) metabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO)-mediated enhancement of complement factor H (CFH) expression and provides a new therapeutic target for patients with GBM.

ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma

November 29, 2021

Nature Cancer [free abstract, subscription required for full article]

Findings from this study suggest that ERK1/2 activation in rGBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype.

Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor-associated macrophages in recurrent glioblastoma

November 26, 2021

Nature Communications [free full-text/open-access]

In this study, researchers set out to characterize tumor-infiltrating immune populations in patients with glioblastoma patients treated with or without neoadjuvant anti-PD-1 checkpoint blockade immunotherapy (neo-aPD1). They found that the tumor microenvironment was heavily dominated by myeloid cells, but in patients treated with neo-aPD1, there was an increase in the density of T cells. Their data suggest that although neo-aPD1 improves survival outcomes by increasing anti-tumor T cell responses, it is not completely curative as this T cell response is curtailed by the engagement of additional T cell checkpoints and other immunosuppressive pathways by the myeloid populations. They postulate that further efforts to increase effector T cell and DC recruitment, in combination with blocking the immunosuppressive signaling engaged by the myeloid cells, will be necessary to achieve clinically relevant effects in recurrent glioblastoma. 

Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial

November 24, 2021

The Lancet Oncology [free abstract, subscription required for full article]

This study is part of an ongoing open-label, single-arm, phase 2 Rare Oncology Agnostic Research (ROAR) basket trial at 27 community and academic cancer centers in 13 countries for patients aged 18 years or older with BRAFV600E mutation-positive high-grade glioma and low-grade glioma. This interim analysis found that Dabrafenib plus trametinib showed clinically meaningful activity in patients with BRAFV600E mutation-positive recurrent or refractory high-grade glioma and low-grade glioma, with a safety profile consistent with that in other indications. BRAFV600E testing could potentially be adopted in clinical practice for patients with glioma.

Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA hubs in cancer

November 24, 2021

Cancer Discovery [free abstract, subscription required for full article]

A new study provides direct evidence for uneven segregation of ecDNA elements in cancers, including most glioblastomas, and sheds new light on mechanisms through which ecDNAs contribute to oncogenesis.

Chimerix Announces Positive ONC201 Data in Recurrent H3 K27M-mutant Diffuse Midline Glioma to Be Presented at the Society for Neuro-Oncology Annual Meeting

November 19, 2021

Chimerix, Inc. [company press release]

In this study, 50 pediatric and adult patients with recurrent H3 K27M DMG who received ONC201 in clinical trials and through expanded access protocols were evaluated for a planned efficacy analysis of overall response rate (ORR) in these patients using the Response Assessment in Neuro-Oncology (RANO) High-Grade Glioma criteria (RANO-HGG). Secondary endpoints included duration of response, time to response, progression-free survival (PFS), overall survival (OS), and ORR using the RANO Low-Grade Glioma criteria (RANO-LGG).The ORR for patients in the study was 20.0% by RANO-HGG criteria and 26.0% by RANO-LGG criteria. Fifteen patients achieved an objective response by RANO-HGG and/or RANO-LGG criteria. Median duration of response was 11.2 months and median time to response was 8.3 months (range 1.9-15.9). PFS at 6 months was 35.1%. With a median follow-up of 18.8 months, median OS was 13.7 months and OS at 24 months was 34.7%. Twenty-five patients had serious adverse events with one possibly related to ONC201 by investigator assessment. Conclusion: ONC201 monotherapy exhibits durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.

Spatiotemporal dynamics of a glioma immune interaction model

November 17, 2021

Nature Scientific Reports [free full-text/open-access]

The authors report a mathematical model which depicts the spatiotemporal dynamics of glioma cells, macrophages, cytotoxic-T-lymphocytes, immuno-suppressive cytokine TGF-β and immuno-stimulatory cytokine IFN-γ through a system of five coupled reaction-diffusion equations.

Multispecific targeting of glioblastoma with tumor microenvironment-responsive multifunctional engineered NK cells

November 9, 2021

PNAS [free abstract, subscription required for full article]

This study demonstrates a promising NK cell-based combinatorial strategy that can target multiple clinically recognized mechanisms of GBM progression simultaneously.

Medium-Chain Acyl-CoA Dehydrogenase Protects Mitochondria from Lipid Peroxidation in Glioblastoma

November 1, 2021

Cancer Discovery [free full-text/open-access]

Researchers uncover a novel protective role for medium-chain acyl-CoA dehydrogenase (MCAD) to clear lipid molecules that may cause lethal cell damage, suggesting that therapeutic targeting of medium-chain fatty acids (MCFA) catabolism may exploit a key metabolic feature of GBM.

Deconvoluting mechanisms of acquired resistance to RAF inhibitors in BRAFv600E-mutant human glioma

November 1, 2021

Clinical Cancer Research [free full-text/open-access]

This study demonstrates that resistance mechanisms to BRAF inhibitors in glioma are varied and may emphasize the need to utilize effective precision combinations of targeted therapy, highlighting the importance of a personalized approach using tumor molecular testing.

BET inhibitors repress expression of interferon-stimulated genes and synergize with HDAC inhibitors in glioblastoma

October 23, 2021

Neuro-Oncology [free full-text/open-access]

Studies identified BET inhibitor-induced vulnerabilities in cancer-relevant pathways, potentially amenable to synergistic combinatorial therapy, such as combination with HDAC inhibitors. The direct inhibitory effect of BET inhibitor on IFN-responsive genes in GBM cells, including CD274, indicates modulation of the tumor immune landscape and warrants further studies.

An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

October 8, 2021

Nature Communications [free full-text/open-access]

Researchers report that studies, collectively, demonstrate that an oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.

Common diabetes drug promising against rare childhood brain tumor in laboratory studies

October 6, 2021

University of Michigan Health Lab [free article]

In a study published in Science Translational Medicine, and funded partly by the CERN Foundation (a program of the National Brain Tumor Society), researchers found that the common diabetes drug, metformin, suppressed tumor growth in group A posterior fossa ependymomas laboratory models.

Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models

October 5, 2021

Cell Reports [free full-text/open-access]

In a retrospective study, ex vivo drug testing based on detecting subtle changes in single-cell mass predicted GBM patient survival at a comparative predictive power as MGMT promoter methylation testing. This “mass” biomarker could be used in situations where genomic biomarkers are unavailable.

Evaluation of a procaspase-3 activator with hydroxyurea or temozolomide against high-grade meningioma in cell culture and canine cancer patients

October 1, 2021

Neuro-Oncology [free abstract, subscription required for full article]

Results from a recent study suggest PAC-1 + TMZ as a potentially efficacious combination for the treatment of human meningioma, and also demonstrate the utility of including pet dogs with meningioma as a means to assess anticancer strategies for this common brain tumor.

Impact of postoperative dexamethasone on survival, steroid dependency, and infections in newly diagnosed glioblastoma patients

October 1, 2021

Neuro-Oncology Practice [free abstract, subscription required for full article]

An analysis of patient records from a single hospital found lower survival, steroid dependency, and higher infection rate in glioblastoma patients associated with higher dexamethasone administration in the initial 3 postoperative weeks. Nearly half of the glioblastoma patients are lymphopenic preoperatively and up to 1 month postoperatively.

MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors

October 1, 2021

Neuro-Oncology [free full-text/open-access]

This first-in-human proof-of-concept study shows MRgFUS enriches the signal of circulating brain-derived biomarkers, demonstrating the potential of the technology to support liquid biopsy for the brain.

Epigenetic encoding, heritability, and plasticity of glioma transcriptional cell states

September 30, 2021

Nature Genetics [free abstract, subscription required for full article]

Single-cell RNA sequencing revealed heritability of malignant cell states, with key differences in hierarchical and plastic cell state architectures in IDH-mutant glioma versus IDH-wildtype glioblastoma, respectively. This work provides a framework anchoring transcriptional cancer cell states in their epigenetic encoding, inheritance, and transition dynamics.

Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response

September 30, 2021

Nature Genetics [free abstract, subscription required for full article]

A new study using single-cell sequencing technology identified an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes for glioma patients.

G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cell immunosuppression and enhances the efficacy of immunotherapy

September 29, 2021

Science Advances [free full-text/open-access]

Researchers demonstrate that granulocyte colony-stimulating factor (G-CSF) reprograms bone marrow granulopoiesis, resulting in noninhibitory myeloid cells within IDH1-mutant glioma tumor microenvironment and enhancing the efficacy of immune-stimulatory gene therapy.

Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas

September 8, 2021

Acta Neuropathologica [free full-text/open-access]

New data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.

The benefit of early surgery on overall survival in incidental low-grade glioma patients: A multicenter study

September 8, 2021

Neuro-Oncology [free abstract, subscription required for full article]

This multicenter study confirms the results of previous studies investigating surgical management of incidental low-grade gliomas and thereby strengthens the evidence in favor of early surgery for these lesions.

A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy

September 3, 2021

Neuro-Oncology [free abstract, subscription required for full article]

Laboratory studies suggest that the drug onvansertib may be effective as monotherapy or in combination with radiotherapy in group 3 medulloblastoma patients.

Intratumoral delivery of STING agonist results in clinical response in canine glioblastoma

August 25, 2021

Clinical Cancer Research [free abstract, subscription required for full article]

A clinical trial in canines showed evidence that activation of STING (Stimulator of INterferon Genes) with a novel immunotherapy called IACS-8779 can trigger a robust, innate anti-tumor immune response in immunologically “cold” tumors such as glioblastoma. 

A clinically applicable integrative molecular classification of meningiomas

August 25, 2021

Nature [free abstract, subscription required for full article]

Researchers introduced four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. 

Brain and other central nervous system tumor statistics, 2021

August 24, 2021

CA: A Cancer Journal for Clinicians [free full-text/open-access]

Incidence rates of adult brain tumors are decreasing; however, 5-year survival rates remain low, according to a new report, funded in part by NBTS, from the Central Brain Tumor Registry of the United States (CBTRUS).

Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors

August 23, 2021

Developmental Cell [free abstract, subscription required for full article]

Researchers describe proof-of-concept studies providing evidence for a potential approach to prevent pediatric low-grade gliomas before tumor-associated neurological damage enters an irreversible phase.

Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment

August 18, 2021

Science Advances [free full-text/openaccess]

Researchers created new laboratory models that recapitulated the glioblastoma tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells. These 3D-bioprinted models could be powerful tools for rapid, reproducible, and robust target discovery; personalized therapy screening; and drug development.

Sustained tumor control with MAPK inhibition in BRAF V600–mutant adult glial and glioneuronal tumors

August 17, 2021

Neurology [free abstract, subscription required for full article]

A retrospective study from patient databases at 6 neuro-oncology departments for adult patients with recurrent or disseminated BRAF V600–mutant glial and glioneuronal tumors, found evidence that RAF and MEK inhibitors may be able to reduce tumor burden and provide long-term clinical benefit for these tumors.

Importance of the intersection of age and sex to understand variation in incidence and survival for primary malignant gliomas 

August 13, 2021

Neuro-Oncology [free full-text/open-access]

To better understand the variation in glioma incidence and survival, investigating the intersection of age and sex is key. This paper, funded partly by the National Brain Tumor Society, shows that the combined impact of these variables is dependent on glioma subtype. These results contribute to the growing understanding of sex and age differences that impact cancer incidence and survival.

Multimodal platform for assessing drug distribution and response in clinical trials

August 12, 2021

Neuro-Oncology [free abstract, subscription required for full article]

Researchers describe a novel tool to assess drug efficacy and patient-specific adaptive responses applicable to pre-clinical and clinical drug development. Data generated using this new approach may inform mechanisms of success and failure in future early phase clinical trials, providing information for optimizing clinical trial design and guiding future application into clinical practice.

Experimental drug targets misbehaving proteins in brain cancer and Alzheimer’s disease

August 3, 2021

Memorial Sloan Kettering Cancer Center website

A paper published in Nature Communications highlights the discovery and development of a new drug that has the ability to potentially detect and reverse protein malfunctions in the central nervous system. The drug is already being tested in a clinical trial for Alzheimer’s disease, and another trial will launch soon for glioblastoma.

Exploring the longitudinal glioma microenvironment landscape uncovers reprogrammed pro-tumorigenic neutrophils in the bone marrow

August 3, 2021

Cell [free full-text/open-access]

A new study suggests that glioblastoma can remotely regulate systemic myeloid differentiation in the bone marrow to generate neutrophils pre-committed to a tumor-supportive phenotype. This work reveals plasticity in the systemic immune host microenvironment, suggesting an additional point of intervention in GBM treatment.

Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial

August 1, 2021

The Lancet Oncology [free abstract, subscription required for full article]

Results were published from an open-label, first-in-human, phase I dose-escalation trial of 12 high-grade glioma patients with newly diagnosed high-grade gliomas who underwent neurosurgical resection followed by injection of a treatment called NSC-CRAd-S-pk7. The findings demonstrate the feasibility and safety of NSC-CRAd-S-pk7, supporting continued investigation.

Characterization of systemic immunosuppression by IDH mutant glioma small extracellular vesicles

July 28, 2021

Neuro-Oncology [free abstract, subscription required for full article]

Tumor-derived extracellular vesicles (exosomes) are garnering increasing attention as a way to understand different aspects of tumor biology such as intratumoral cell signaling and tumor interactions with the tumor microenvironment. In this study, the authors report an increase in circulating monocytes and a decrease in tumor-infiltrating lymphocytes in mice after systemic administration of exosomes harvested from IDH-mutant glioma cells versus exosomes from IDH–wild-type cells. The findings in this study provide evidence of the role of IDH-mutant glioma exosomes in modulating the tumor microenvironment.

An immunotherapy drug trial expands across the nation to advance research

July 28, 2021

NCI website [news article]

NCI-CONNECT, an initiative NBTS partners with, launched an immunotherapy drug trial across its national network of collaborative institutions to reach more people with rare brain and spine tumors, more rapidly determine if the therapy is effective, and set the foundation for future trials. Learn the impact of this first-of-its-kind trial.

EANO guideline on the diagnosis and management of meningiomas

July 28, 2021

Neuro-Oncology [free abstract, subscription required for full article]

This paper details the European Association of Neuro-Oncology’s (EANO) updated recommendations for the diagnosis and treatment of meningiomas.

Scientists can detect brain tumors using a simple urine or blood plasma test

July 26, 2021

MedicalExpress [University of Cambridge press release]

Researchers from the Cancer Research UK Cambridge Institute have developed two tests that can detect the presence of glioma, a type of brain tumor, in patient urine or blood plasma. Although the research, published in EMBO Molecular Medicine, is in its early stages and only a small number of patients were analyzed, the team say their results are promising.

Survival rates among adolescents and young adults with brain tumors sees uptick

July 26, 2021

HemOnc Today [news article]

Results showed significant improvement in 5-year relative survival for brain and other nervous system tumors, according to findings published in the journal Cancer by National Cancer Institute researchers using data from the SEER database and National Center for Health Statistics.

Efficacy of carboplatin and isotretinoin in children with high-risk medulloblastoma

July 22, 2021

Journal of the American Medical Association [free abstract, subscription required for full article]

For children with high-risk group 3 medulloblastoma, therapy intensification with the chemotherapy carboplatin improves event-free survival, according to a study published online July 22 in JAMA Oncology.

For kids with medulloblastoma, trial suggests radiation can be tailored

July 16, 2021

National Cancer Institute website

Results of a large clinical trial suggest that some kids with medulloblastoma can safely get less radiation without limiting their long-term survival, whereas others may need the standard doses. 

Reversing epigenetic gene silencing to overcome immune evasion in CNS malignancies

July 15, 2021

Frontiers in Oncology [free full-text/open-access]

Researchers report results from a study evaluating the ability of a drug called GSK12 to help improve the efficacy of immunotherapy when combined with immune checkpoint inhibitor treatment. The authors found that in laboratory models of glioblastoma, using GSK126 could improve current immunotherapy strategies by reversing the epigenetic changes that enable immune cell evasion leading to enhanced immune cell trafficking to the tumor.

What you need to know about the new brain tumor classification and grades

July 15, 2021


The World Health Organization (WHO) sponsors a group of pathologists and clinicians who are experts in brain and spinal cord tumors to develop the criteria for how brain tumors are classified and graded. As the scientific field continues to better understand the biology of brain tumors, a separate organization, cIMPACT (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy), periodically reviews and updates new recommendations that guide the WHO’s brain tumor classifications.

The latest round of revisions to the WHO classifications for brain tumors will officially be published later this year, and leaders of the process to update the classification have published a review article that previews the updates.

Inhibition of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme of the nicotinamide adenine dinucleotide salvage pathway, to target glioma heterogeneity through mitochondrial oxidative stress

July 14, 2021

Neuro-Oncology [free abstract, subscription required for full article]

An enzyme called NAMPT is overexpressed in most malignancies, including gliomas, and can serve as a tumor-specific target. In this study, researchers demonstrated that blocking NAMPT with a drug called KPT9274 warrants further evaluation as a potential therapeutic strategy against gliomas.

FDA releases final guidance on evaluating cancer drugs for CNS metastases

July 8, 2021

CancerNetwork [news article]

A final guidance was released by the FDA, titled, “Evaluating Cancer Drugs in Patients with Central Nervous System Metastases: Guidance for Industry,” which details the optimal design for clinical trials evaluating drugs and biological products for patients with central nervous system (CNS) metastases.

The guidance details important considerations for trials involving systemic therapies for this patient population should the agent’s label describe anti-tumor activity in the CNS. Further considerations referenced in the guidance include ideal patient populations, available therapies, and prior therapies, as well as noting that trial designs need to take prior therapies into consideration and better plan for assessing CNS metastases.

Systems pharmacogenomics identifies novel targets and clinically actionable therapeutics for medulloblastoma

July 7, 2021

Genome Medicine [free full-text/open-access]

A new genetic map may help researchers identify drugs that could be repurposed and tested as an effective treatment for medulloblastoma.

Q&A: Keto diet intervention effective in small study of patients with glioma

July 7, 2021

HemOnc Today [news article]

Patients with glioma who completed the 8-week GLioma Atkins-based Diet (GLAD) experienced “meaningful” ketonuria and significant systemic and cerebral metabolic changes, according to results from a small study published in Neurology. More work is needed to determine whether this type of diet will be helpful for patients and, if so, when it could be incorporated best into treatment.

Genome-wide DNA methylation landscape reveals glioblastoma’s influence on epigenetic changes in tumor-infiltrating CD4+ T cells

July 5, 2021

Oncotarget [free full-text/open-access]

A study published in Oncotarget suggests that glioblastoma might induce epigenetic alterations in tumor-infiltrating CD4 T-cells, thereby influencing anti-tumor immune response by manipulating differentiation and function of tumor-infiltrating CD4 T-cells.

Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma

July 5, 2021

Nature Communications [free full-text/open-access]

Researchers describe lymph node-like structures discovered close to gliomas, where immune cells can be activated to attack the tumor. They also found that immunotherapy enhanced the formation of these structures in a mouse model. This discovery suggests new opportunities to regulate the anti-tumor response of the immune system.

Inhibiting DNA-PK induces glioma stem cell differentiation and sensitizes glioblastoma to radiation in mice

June 30, 2021

Science Translational Medicine [free abstract, subscription required for full article]

Glioma stem cells promote progression and therapeutic resistance of glioblastoma and are maintained by core transcription factors, including SOX2. In this paper, researchers identify DNA-dependent protein kinase (DNA-PK) as crucial for SOX2 stability and maintenance of glioma stem cells. Blocking DNA-PK with the drug NU7441 led to tumor regression and prolonged survival in laboratory models and sensitized glioblastoma xenografts to radiotherapy. This suggests that DNA-PK has potential as a therapeutic target for treating glioblastoma.

Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1

June 29, 2021

Nature Communications [free full-text/open-access]

A study published in Nature Communications describes a potentially new way to analyze and compare patient tumor tissue samples by combining mathematical models using machine-learning-based image analysis and multiplex spatial protein profiling. The researchers then used this tool to reveal similarities shared between glioblastoma and melanoma, immunosuppressive factors that are unique to the glioblastoma microenvironment, and potential co-targets for enhancing the efficacy of neoadjuvant immune checkpoint blockade.

The effects of palbociclib in combination with radiation in preclinical models of aggressive meningioma

June 24, 2021

Neuro-Oncology Advances [free full-text/open-access]

Researchers report that data from preclinical studies suggest that the drug palbociclib could be repurposed to treat patients with p16-deficient, Rb-intact meningiomas, and that a clinical trial in combination with radiation therapy merits consideration.

Tumor-associated hematopoietic stem and progenitor cells positively linked to glioblastoma progression

June 23, 2021

Nature Communications [free full-text/open-access]

A study published in Nature Communications identifies how blood stem cells make brain tumors more aggressive, an important element in the complex landscape of immune cells surrounding glioblastomas that may serve as a target for brain tumor immunotherapies.

Notch1 switches progenitor competence in inducing medulloblastoma

June 23, 2021

Science Advances [free abstract, subscription required for full article]

New research suggests that the Notch1 pathway plays a critical role in group 3 medulloblastoma initiation.

Clinical characterization of adult medulloblastoma and the effect of first-line therapies on outcome; The MD Anderson Cancer Center experience

June 22, 2021

Neuro-Oncology Advances [free full-text/open-access]

Researchers from MD Anderson Cancer Center examined data from 200 adult medulloblastoma patients treated at the hospital from 1978-2017 and identified standard-risk status, first-line radiation and adjuvant chemotherapy as factors associated with improved outcomes.

Opening of the blood–brain barrier using low-intensity pulsed ultrasound enhances responses to immunotherapy in preclinical glioma models

June 21, 2021

Clinical Cancer Research [free abstract, subscription required for full article]

Preclinical research found that low-intensity pulsed ultrasound increases immune therapeutic delivery to the tumor microenvironment with an associated increase in survival and is an emerging technique for enhancing novel therapies in the brain.

Overcoming immune suppression in glioblastoma with engineered NK cells

June 21, 2021

Genetic Engineering & Biotechnology News (GEN) [news article]

Preclinical research from the University of Texas MD Anderson Cancer Center demonstrated that although glioblastoma stem cells (GSCs) can be targeted by natural killer (NK) cells, they are able to evade immune attack by releasing the TFG-β signaling protein, which blocks NK cell activity. Deleting the TFG-β receptor in NK cells, however, rendered them resistant to this immune suppression and enabled their anti-tumor activity. The findings are published in the Journal of Clinical Investigation.

SMARCB1 deletion in atypical teratoid rhabdoid tumors results in human endogenous retrovirus K (HML-2) expression

June 18, 2021

Nature Scientific Reports [free full-text/open-access]

A new study demonstrates that AT/RT tumor formation is aided by aberrant HML-2 activation, which is dependent on SMARCB1 and its interaction with MYC.

Yale Cancer Center Laboratory Study Shows Combination Treatment Effective in IDH Mutant Cancers

June 17, 2021

Yale Medicine press release

A new study led by Yale Cancer Center scientists, and funded with NBTS pilot grants, revealed the combination of ATR and PARP inhibitor therapies can effectively target the enzyme (IDH-1/2) in mutant cancer cells. The findings could help minimize toxicities from drug treatment for patients with cancer. The research is published online in the journal NAR Cancer

Servier announces promising phase I data for vorasidenib in IDH mutant low-grade glioma published in Clinical Cancer Research

June 16, 2021

Company press release

The journal Clinical Cancer Research has published data from a phase I study evaluating single-agent vorasidenib in isocitrate dehydrogenase (IDH) mutant advanced solid tumors, including low-grade glioma. Vorasidenib demonstrated both a favorable safety profile and preliminary clinical activity in recurrent or progressive IDH1/2 mutant low-grade glioma. 

Enhancing proteasomal processing improves survival for a peptide vaccine used to treat glioblastoma

June 16, 2021

Science Translational Medicine [free abstract, subscription required for full article]

The synthetic peptide vaccine called pepVIII, targeting EGFRvIII, has shown promising early results in glioblastoma patients. Publishing in Science Translational Medicine researchers now have found that a tyrosine substitution (Y6-pepVIII) improved the efficacy of the vaccine in mice by increasing proteasome cleavage. Y6-pepVIII in combination with anti–PD-1 therapy increased survival compared to the checkpoint blockade therapy alone. The results suggest that a similar optimization strategy could be effective in improving treatment efficacy of other peptide vaccines.

Yale Cancer Center study reveals new pathway for brain tumor therapy

June 15, 2021

EurekaAlert [press release]

In a new study led by Yale Cancer Center, researchers show the nucleoside transporter ENT2 may offer an unexpected path to circumventing the blood-brain barrier (BBB) and enabling targeted treatment of brain tumors with a cell-penetrating anti-DNA autoantibody called DX1.

P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas

June 14, 2021

Nature Communications [free full-text/open-access]

In this study, researchers identified p32/gC1qR/HABP/C1qBP to be specifically expressed on the surface of glioma cells, making it a suitable tumor-associated antigen for redirected CAR T cell therapy. The authors then generated p32 CAR T cells and found them capable of recognizing and specifically eliminating p32 expressing glioma cells and tumor-derived endothelial cells and to control tumor growth in lab models. Thus, p32 CAR T cells may serve as a therapeutic option for glioblastoma patients.

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

June 14, 2021

Cell [free abstract, subscription required for full article]

Researchers used single-cell sequencing methods to help explore how glioblastoma tumors interact with immune cells in their microenvironment. Results demonstrate that macrophages induce a transition of glioblastoma cells into mesenchymal-like (MES-like) states and highlight extensive alterations of the immune microenvironment with potential therapeutic implications

Pediatric Medulloblastoma Subgroups May Benefit from Lower-Dose Radiation Therapy

June 11, 2021

GenomeWeb [news article]

Researchers hoping to validate that treatment with a lower dose of craniospinal irradiation (CSI) is effective for children with medulloblastoma found that patients with certain genetic alterations responded better to the lower dose, according to a study published in the Journal of Clinical Oncology on Thursday. 

Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40

June 8, 2021

Nature Communications [free full-text/open-access]

Preclinical research published in the journal Nature Communications suggests that an antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting opportunities for GBM and other solid tumors.

IN8bio completes treatment of first cohort in phase I clinical trial with gamma delta T-cell therapy in patients with newly diagnosed glioblastoma

June 7, 2021

2021 ASCO Annual Meeting [press release]

An update from the ongoing phase 1 clinical trial of INB-200, a genetically modified gamma delta T-cell therapy, in patients with newly diagnosed glioblastoma was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. INB-200 was co-administered to patients undergoing the standard-of-care therapy for GBM during the temozolomide (TMZ) maintenance treatment. The therapy was well-tolerated with no observed infusion reactions, cytokine release syndrome (CRS), neurotoxicity or dose limiting toxicities (DLTs) and cleared a data safety monitoring board (DSMB) review. Enrollment for cohort 2 has been initiated. 

Y-mAbs announces update on omburtamab for DIPG

June 4, 2021

2021 ASCO Annual Meeting [press release]

Initial results from a small phase I dose-escalation study of the drug omburtamab presented at the 2021 ASCO Annual Meeting found the treatment to be well-tolerated with positive early signs of efficacy as compared to the historical controls. 

Ivy Brain Tumor Center announces interim results from a phase 0 ‘trigger’ trial of targeted combination therapy for glioblastoma

June 2, 2021

2021 ASCO Annual Meeting [press release]

Initial results from an ongoing phase 0 study (NCT04391595) evaluating the tumor pharmacokinetics (PK) and tumor pharmacodynamics (PD) of abemaciclib, a selective CDK4/6-inhibitor, plus LY3214996, a selective ERK1/2 inhibitor, in recurrent glioblastoma patients demonstrates that Abemaciclib and LY3214996 achieve pharmacologically-relevant concentrations in tumor tissue.

Epigenomic landscape and 3D genome structure in pediatric high-grade glioma

June 2, 2021

Science Advances [free full-text/open-access]

Research recently published in the journal Science Advances finds that three-dimensional genome alterations may play a critical role in the pHGG epigenetic landscape and contribute to tumorigenesis.

PARP-mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma 

June 1, 2021

Neuro-Oncology [free full-text/open-access]

An NBTS-funded study demonstrates that drugs called PARP inhibitors could be combined with temozolomide chemotherapy to benefit patients with MGMT-unmethylated glioblastoma.

Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study

June 1, 2021

The Lancet Oncology [free abstract, subscription required for full article]

The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. A second interim analysis of data from the trial suggests that adjuvant temozolomide chemotherapy, but not concurrent temozolomide chemotherapy, was associated with a survival benefit in patients with 1p/19q non-co-deleted anaplastic glioma. Clinical benefit was dependent on IDH1 and IDH2 mutational status.

Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer

May 27, 2021

Nature Genetics [free abstract, subscription required for full article]

The NBTS-funded GLASS consortium analyzed a large set of samples of primary glioma tumors before and after treatment with radiation. Researchers identified patterns in how certain tumors change after radiation and which tumors become more aggressive. This research underscores the importance of tumor DNA damage repose and may be leveraged to predict sensitivity to radiation therapy in recurrent cancer.

Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance

May 27, 2021

Nature Biomedical Engineering [free abstract, subscription required for full article]

A recent study suggests that the combination of anticancer drugs with distinct mechanisms of action with selective drug release and convection-enhanced delivery may represent a translational strategy for the treatment of TMZ-resistant gliomas.

NF1 mutation drives neuronal activity-dependent initiation of optic glioma

May 26, 2021

Nature [free abstract, subscription required for full article]

Fifteen percent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome develop optic pathway gliomas (OPGs) during early childhood. New research demonstrates that stimulation of optic nerve activity increases optic glioma growth, that decreasing visual experience via light deprivation prevents tumour formation and maintenance, and that pharmacological blocking a protein called NLGN3 can halt the formation and progression of Nf1-OPGs.

Glioblastoma study discovers protective role of metabolic enzyme, revealing a novel therapeutic target

May 26, 2021

EurekAlert [press release]

Researchers at The University of Texas MD Anderson Cancer Center have discovered a novel function for a metabolic enzyme called “MCAD” in glioblastoma (GBM). Preclinical findings published in the journal Cancer Discovery reveal an important new understanding of metabolism in GBM and support the development of MCAD inhibitors as a novel treatment strategy. 

Modified RANO affords a more accurate assessment of outcomes in recurrent glioblastoma

May 26, 2021

OncLive [news article]

New results from a clinical trial suggested that using a modified version of the Response Assessment in Neuro-Oncology (RANO) criteria called Modified RANO may be the optimal way to measure tumor response to treatment for recurrent glioblastoma patients.

Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas

May 24, 2021

Nature Cancer [free full-text/open-access]

The authors identify a potential metabolic mechanism to augment the response to immunotherapy in IDH-mutant gliomas.

Tumor-promoting immune cells retrained to fight most aggressive type of brain cancer

May 11, 2021

Nature Communications [free full-text/open-access]

A study published in Nature Communications shows how glioblastomas effectively hamper the action of treatments developed to activate the body’s own immune system to fight tumors, but that “reprogramming” a type of immune cell known as “Tregs” could be an effective strategy to overcome immunosuppression in glioblastoma tumors. 

Dabrafenib-trametinib combination active in BRAF V600E-mutant glioma

May 8, 2021

HemOnc Today

Findings presented during the virtual American Association for Cancer Research Annual Meeting suggest that a combination of the drugs dabrafenib and trametinib may benefit patients with high-grade or low-grade gliomas whose tumors have recurred and have a mutation known as BRAF V600E

Innovating brain tumor clinical trials: lessons learned during COVID-19

May 7, 2021

Neuro-Oncology/NBTS Blog

Did the COVID-19 pandemic offer any silver linings for brain tumor research? NBTS staff led a workshop and subsequent research paper, just published, to explore if new flexibilities and changes to the operation of clinical trials during COVID-19 may actually benefit patients hoping to participate in research studies after the pandemic ends.

Inovio is going after the ‘impossible tumor’ left in the dust of new cancer meds

May 7, 2021

Fierce Biotech

A biotech is conducting a phase I clinical trial called GBM-001 that will provide early data on a combination strategy using its DNA-based treatments INO-5401 and INO-9012 and Regeneron-Sanofi’s PD-1 inhibitor Libtayo. 

A subset of PARP inhibitors induces lethal telomere fusion in ALT-dependent tumor cells

May 5, 2021

Science Translational Medicine [free abstract, subscription required for full article]

The alternative lengthening of telomere (ALT) is a mechanism used by some tumors, including most lower-grade astrocytomas, to stabilize their telomeres and survive. Researchers studied ALT-associated tumors and showed that they shared hypersensitivity to a subgroup of drugs known as PARP inhibitors, suggesting this treatment approach might be effective in patients with ALT-dependent tumors.

Environmental and sex-specific molecular signatures of glioma causation

May 4, 2021

Neuro-Oncology [free full-text/open-access]

In a study funded partly by grants from the NBTS, researchers found that cancer-causing mutations in glioma primarily originated as a consequence of internal rather than external factors, and that potentially tumor-seeding mutations have different roles in males versus females. Additionally, a rare environmental risk factor was suggested for some cases of glioma, particularly in males.

Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas

April 29, 2021

Neuro-Oncology [free abstract, subscription required for full article]

Studies done in mice suggest that anti-CSF1/CSF1R antibody treatment may be an effective normalization cancer immunotherapy strategy to treat malignant meningiomas.

SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models

April 28, 2021

Science Translational Medicine [free abstract, subscription required for full article]

Researchers developed a new type of CAR T cell treatment (a type of immunotherapy) called synNotch-CAR T cells. In laboratory studies, including ones done in mice with glioblastoma tumors, the authors demonstrated that synNotch-CAR T cells were better at controlling tumors than traditional CAR T cells and did not result in toxicity or damage to healthy tissue. (Related articles, here and here).

EGFR activates a TAZ-driven oncogenic program in glioblastoma

April 28, 2021

Cancer Research [free abstract, subscription required for full article]

Preclinical laboratory research identified a transcription factor known as TAZ as a potential biomarker of sensitivity to the drug osimertinib in GBM tumors with EGFR alterations.

Immunotherapy combination shows early promise in aggressive brain cancers

April 13, 2021

The Institute of Cancer Research [presentation at AACR]

A small phase I trial known as “Ice-CAP” is testing the effect of combining the immunotherapy drug atezolizumab with the precision drug ipatasertib for glioblastoma patients who have relapsed after treatment. Initial results presented at the American Association of Cancer Research (AACR) Annual Meeting showed that two of the first 10 patients treated in the trial, each with loss of the PTEN gene, responded to treatment.

The white matter is a pro-differentiative niche for glioblastoma

April 12, 2021

Nature Communications [free full-text/open-access]

Researchers found that glioblastoma mimics an injury response in the brain and that exploiting this process may offer treatment opportunities for a subset of patients.

Proteogenomic and metabolomic characterization of human glioblastoma

April 12, 2021

Cancer Cell [free full-text/open-access]

Recent work from the NCI-funded Clinical Proteomic Tumor Analysis Consortium highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment.

Oncolytic therapy using modified herpesvirus shows promise for pediatric high-grade glioma

April 11, 2021

HemOnc Today [news article]

Use of a modified herpesvirus with and without radiation showed promising efficacy and safety for the treatment of children with recurrent or progressive high-grade glioma, according to results of a phase 1 trial published recently in the New England Journal of Medicine.

Living with a central nervous system (CNS) tumor: findings on long-term survivorship from the NIH Natural History Study

April 10, 2021

Neuro-Oncology Practice [free full-text/open-access]

A study of long-term survivors on brain tumors finds that these individuals fall into distinct cohorts with either no significant symptoms or very high symptom burden, regardless of tumor grade or mutational profile. The authors write that this data demonstrates the need for survivorship care programs and future studies to explore the symptom trajectory of all CNS tumor patients for prevention and early interventions.

De novo purine biosynthesis is a major driver of chemoresistance in glioblastoma

April 4, 2021

Brain [free abstract, subscription required for full article]

Research published in the journal Brain suggests that blocking the activity of a target called IMPDH2 by repurposing an already FDA-approved drug called mycophenolate mofetil may enhance the effectiveness of temozolomide in glioma patients. 

Cancer may be driven by DNA outside of chromosomes

April 1, 2021

The Scientist

NBTS-funded researcher Dr. Paul Mischel authored an article about his discovery of “extrachromosomal DNA,” which he studied as part of NBTS’s Defeat GBM Research Collaborative

Cancer-specific loss of TERT activation sensitizes glioblastoma to DNA damage

March 30, 2021

PNAS [free full-text/open-access]

New findings provide insights into the mechanism of cancer-specific TERT regulation, uncover rapid effects of GABPB1L-mediated TERT suppression in GBM maintenance, and establish GABPB1L inhibition in combination with chemotherapy as a therapeutic strategy for TERT promoter mutant GBM.

Accelerating glioblastoma therapeutics via venture philanthropy

March 30, 2021

Drug Discovery Today [free full-text/open-access]

National Brain Tumor Society staff and board members teamed up with internationally-renown financial expert and MIT professor, Dr. Andrew Lo, on a new paper published in Drug Discovery Today that demonstrates the promise of leveraging venture philanthropy (or a “megafund”) to stimulate and fund more drug development for glioblastoma.

Zika Virus helps kill deadly brain cancer in mice
March 29, 2021
The Zika virus can activate immune cells to destroy glioblastoma, an aggressive brain cancer, a new study with mice shows.
P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression
March 26, 2021
Nature Communications [free full-text/open-access]
Researchers found that a cell adhesion molecule called “P-selectin” mediates glioblastoma proliferation and invasion by altering microglia/macrophages activation state and leading to suppression of the immune system.
Watch: Microrobots fight brain tumors in mice
March 24, 2021
Scientists have created a microrobot that can pass the near-impenetrable blood-brain barrier to treat brain tumors in mice, they report in a new study in Science Robotics.
A vaccine targeting mutant IDH1 in newly diagnosed glioma
March 24, 2021
[free full-text/open-access]
Data from a small phase I clinical trial in Europe were recently published in the journal Nature. Thirty-three patients with newly diagnosed glioma with mutations to their IDH1 gene were treated with a vaccine-based immunotherapy targeting these mutations in a trial called NOA16. NOA16 met its primary endpoints by demonstrating the safety and immunogenicity of the IDH1 vaccine in patients. Vaccine-induced immune responses were observed in 93.3% of patients.
The transcriptional landscape of Shh medulloblastoma
March 19, 2021
Nature Communications [free full-text/open-access]
A large team of researchers from multiple institutions published a study observing differences among molecular subtypes of sonic hedgehog medulloblastoma (Shh-MB) and highlight the key roles of specific pathways in the pathogenesis of Shh-MB and open up opportunities for therapeutic intervention.
Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations
March 19, 2021
Acta Neuropathologica
[free full-text/open-access]
A large team of researchers from multiple institutions published a study observing that non-R132H IDH1/2-mutated astrocytomas have a more favorable prognosis than their IDH1R132H mutated counterpart, indicating that not all IDH-mutations in gliomas are identical. This difference is clinically relevant and should be taken into account for patient prognostication.
N-cadherin upregulation mediates adaptive radioresistance in glioblastoma
March 15, 2021
Journal of Clinical Investigation
[free full-text/open-access]
Researchers at the University of Alabama at Birmingham performed studies in animal models and human and mouse cells, which indicate that an adhesive cell surface protein known as N-cadherin — or N-cad — may be key in overcoming glioblastoma’s resistance to radiation therapy.
Novel gene-silencing RNA drug shows promise in glioblastoma
March 10, 2021
Fierce Biotech
Scientists at Northwestern University have developed a drug —dubbed NU-0129 and consisting of a gold nanoparticle core densely packed with small interfering RNA (siRNA) — that targets the cancer-promoting Bcl2L12 gene in glioblastoma tumors. A small “phase 0” clinical trial, published in Science Translational Medicine, showed it could penetrate the blood-brain barrier, suggesting that the experimental drug, also known as a spherical nucleic acid (SNA) drug, should undergo further testing to verify its safety and therapeutic effect.

Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signaling

March 4, 2021
Nature Cell Biology [free abstract, subscription required for full article]
Circular RNAs regulate a variety of biological processes. Now an unexpected cell signaling pathway in cancer cells is revealed in which a translated circular RNA derived from E-cadherin pre-mRNA activates EGFR signaling in glioblastoma cancer stem cells and acts as a ligand for the EGFR mutant EGFRVIII, a common oncogenic variant.
A company is developing tiny, remote-controlled devices, built to travel through into the brain and deliver a dose of medicine where it’s needed the most: at the site of the tumor.
Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis
February 15, 2021
[free abstract, subscription required for full article]
The authors used single-cell sequencing techniques to create an atlas of T cells in gliomas and highlighted CD161 and other NK cell receptors as immunotherapy targets.
PRMT5 inhibition disrupts splicing and stemness in glioblastoma
February 12, 2021
Nature Communications
[free full-text/open-access]
The authors report on a new rationale for developing brain-penetrant PRMT5 inhibitors as a treatment for glioblastoma.
This article discusses progress being made by a company developed specifically to make new treatments for pediatric brain cancer.
H3.3-K27M drives neural stem cell-specific gliomagenesis in a human iPSC-derived model
February 4, 2021
Cancer Cell
[free abstract, subscription required for full article]
NBTS-funded researchers studied the effects of H3K27M, a frequent pediatric glioma driver mutation, in different DIPG-relevant cell types and found the mutation upregulated certain developmental genes, producing diverse outcomes in different stem and progenitor cell types.
Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma
January 20, 2021
Science Translational Medicine
[free abstract, subscription required for full article]
To identify better treatments for high-risk medulloblastoma, the authors screened more than 3000 compounds using six different human cell lines and showed that inhibitors of cell cycle checkpoint kinases (CHK1/2) increased could be used to increase the efficacy of standard chemotherapeutics for treating these tumors.
The latest quarterly report from the National Brain Tumor Society providing a summary of the clinical trials that have recently opened or started enrolling for primary brain tumor patients in the United States.
This study reports that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients.
Pten Deficiency Leads To Proteasome Addiction, A Novel Vulnerability In Glioblastoma
January 11, 2021
[free abstract, subscription required for full article]
This NBTS-funded study found that proteasome inhibition is a potential synthetic lethal therapeutic strategy for GBM with proteasome addiction due to a high protein synthesis rate and autophagy deficiency.
The revolutionary GBM AGILE adaptive clinical trial platform is opening two new treatment arms, with one evaluating Kintara Therapeutics’s chemotherapy, VAL-083, and Kazia Therapeutics’s targeted therapy, paxalisib.
Glioblastoma Linked with Brain Healing after Trauma
January 5, 2021
Genetic Engineering and Biotechnology News (GEN)

Studies by researchers in Canada suggest that the healing process that follows a brain injury—such as trauma, infection or stroke—could spur the growth of glioblastoma tumors, when new cells generated to replace those lost to the injury are derailed by mutations.


4 Big Takeaways From the 2020 Annual Meeting of the Society for Neuro-Oncology
December 19, 2020

National Brain Tumor Society staff distill the key takeaways from the 2020 Annual Meeting of the Society for Neuro-Oncology that have the potential to shape the future of the brain tumor research and treatment landscape for years to come.

Inhibition of 2-hydroxyglutarate elicits metabolic reprogramming and mutant IDH1 glioma immunity in mice
December 17, 2021
Journal of Clinical Investigation
[free full-text]

This work focuses on glioma subtypes harboring mIDH1, TP53, and ATRX inactivation. The authors combined D-2HG inhibition/IR/TMZ with anti–PDL1 immune checkpoint, and demonstrated that metabolic reprogramming elicits anti–mIDH1 glioma immunity, leading to increased MS and immunological memory.

Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis
December 10, 2020
[free abstract, subscription required for full article]

This study found that an estimated 50% of gliomas with H3.3G34 mutations also carry activating PDGFRA mutations, which may be more potent and targetable drivers of tumor growth than G34R/V.