Brain Tumor Research News & Updates
2021
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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]
March 24, 2021
Nature [free full-text/open-access]
March 19, 2021
Nature Communications [free full-text/open-access]
March 19, 2021
Acta Neuropathologica [free full-text/open-access]
March 15, 2021
Journal of Clinical Investigation [free full-text/open-access]
March 3, 2021
Fierce Biotech
February 15, 2021
Cell [free abstract, subscription required for full article]
February 12, 2021
Nature Communications [free full-text/open-access]
February 10, 2021
ENDPOINTS News
February 4, 2021
Cancer Cell [free abstract, subscription required for full article]
January 20, 2021
Science Translational Medicine [free abstract, subscription required for full article]
January 13, 2021
Nature Communications [free full-text/open-access]
January 11, 2021
Neuro-Oncology [free abstract, subscription required for full article]
January 7, 2021
NBTS Blog
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.
2020
4 Big Takeaways From the 2020 Annual Meeting of the Society for Neuro-Oncology
December 19, 2020
NBTS Blog
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
Cell [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.
