Brain Tumor Research News & Updates

Research Progress


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.

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.

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

June 17, 2021

Yale Medicine

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.

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.

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.

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.

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

April 11, 2021HemOnc Today

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.

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.  

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.