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This is an interesting example of how advances against glioblastoma may come from **combining treatments rather than continually searching for a single “magic bullet.”** Researchers are studying whether extracellular vesicles – tiny particles that can cross the blood-brain barrier – can make glioblastoma cells more vulnerable to CAR T-cell therapy. They are using mathematical modeling and sophisticated image analysis to understand exactly how the two interact.
This is an interesting approach that makes a lot of sense. After glioblastoma surgery, we usually wait several weeks for the surgical wound to heal before starting radiation and chemotherapy. Unfortunately, glioblastoma does not wait.
Disclaimer: GT Medical is a proud sponsor of the Musella Foundation!
This is an interesting new approach that is now making the important jump from laboratory studies into its **first human trial**.
This is an interesting new approach, but it is important to understand that it is still at the **preclinical research stage**—there is not yet a drug being tested in glioblastoma patients.
The investigational treatment NEO100, a highly purified form of perillyl alcohol, showed encouraging preliminary results in a Phase IIa trial for patients with recurrent or progressive IDH1-mutant grade 3 or 4 gliomas. The NEO100 treatment is self-administered by patients through the nose four times a day, using a nasal mask and nebulizer, with the intranasal delivery intended to help overcome the blood-brain barrier. In the single-arm study, 24 patients received treatment in 28-day cycles; researchers compared the results with historical results for patients receiving treatment for recurrent high-grade glioma.
The study met its primary endpoint, with 49% of patients progression-free at six months (compared with an expected 20% based on the study's historical benchmark). Median overall survival was reported as 26 months, with 87% of patients alive at six months, 61% at one year, and 54% at two years. Five patients were still receiving treatment when the preliminary results were reported, including one who had remained progression-free for 19 months, and the company reported several radiographic responses, including one patient whose enhancing tumor largely resolved after prolonged treatment. NEO100 was reportedly well tolerated, with the company describing no significant toxicity even with prolonged treatment, although the full safety and efficacy data have not yet been published in a peer-reviewed journal.
It is important to note that this was a small, non-randomized trial, and our understanding of the prognosis of recurrent IDH1-mutant tumors continues to evolve (for example, recent research suggests that acquired RAS-MAPK mutations may be associated with shorter survival). Despite these caveats, the results are encouraging for a disease with no approved targeted therapies and very few salvage options in the recurrent setting. The company plans to meet with the FDA to discuss the next steps and a potential registrational trial.
The ETERNITY study looked at 185 people who had survived at least 5 years after a diagnosis of glioblastoma, IDH-wildtype, or grade 4 IDH-mutant astrocytoma, with patients surviving an average of about nine years. The researchers found that 78% had some measurable impairment in at least one area of thinking or memory. The most common difficulties involved processing speed, mental flexibility, and finding words, while recognition memory was less often affected. Importantly, however, cognitive function was mostly stable over time; the only consistent decline seen across the group was a small worsening in the ability to recall verbal information after a delay. Tumor location mattered; tumors involving the left side of the brain were associated with poorer verbal memory and word fluency, while temporal lobe involvement was particularly associated with memory difficulties. Patients who had experienced multiple tumor recurrences also tended to have worse cognitive flexibility. For patients and families, the findings are encouraging in that surviving many years does not necessarily mean that cognitive abilities will continue to decline, although some lasting difficulties may remain after the tumor and its treatment have affected the brain. The study did not evaluate potential treatments for the cognitive deficits observed, but the authors emphasized that regular neurocognitive monitoring and greater attention to preserving cognitive function should be an important focus of long-term care.
A new preclinical study from Stanford has added to the growing understanding of how gliomas leverage normal brain activity for growth. Researchers found that NLGN3, a protein made by normal neurons, interacts with the CSPG4 protein found on glioma cells, activating a mechanosensing pathway involving PIEZO1 that ultimately promotes tumor growth. This discovery broadens potential treatment targets beyond NLGN3 itself, possibly to CSPG4; however, the major challenge is that this pathway also appears to help maintain normal oligodendrocyte precursor cells, so blocking it could potentially interfere with healthy brain function. Nevertheless, this work provides important new insights into how gliomas exploit neuronal activity and could help researchers find ways to disrupt this process without harming normal neuron-glial signaling the brain needs.
Our next webinar is this Thursday, August 13th at 7pm ET. The topic is "Multi-antigen T-cell therapy in pediatric brain tumors" with Dr. Eugene Hwang. To join, visit virtualtrials.org/webinar.
A randomized phase III trial from the Netherlands compared an ultra-short radiation schedule (6 treatments of 6 Gy over 2 weeks) with standard radiation for newly diagnosed glioblastoma (30 treatments of 2 Gy over 6 weeks). Both groups received concurrent temozolomide followed by adjuvant temozolomide.
The study enrolled only 135 of the planned 474 patients due to slow recruitment. Even so, the results were concerning. Median overall survival was 13 months with the 2-week schedule versus 21 months with the standard schedule. The 6 × 6 Gy regimen also produced more radiation necrosis or pseudoprogression (47.8% vs 16.2%), and patients receiving the ultra-short treatment were more likely to require dexamethasone later.
It's worth noting that these results do not mean that all shortened radiation schedules are inferior. The Perry regimen, for example, uses 40 Gy in 15 treatments over 3 weeks and is an established option for selected older patients who may not be ideal candidates for the standard 6-week course. However, this study suggests that compressing radiation into just 6 very high-dose treatments is not advised for the general newly diagnosed GBM population.
A recent University of Miami study looked at 44 patients with butterfly high-grade gliomas (tumors that cross the corpus callosum and involve both sides of the brain). These tumors can be difficult to safely remove with resection surgery.
In the study, 29 patients received laser interstitial thermal therapy (LITT) and 15 had biopsy alone. Median overall survival was 14.9 months with LITT versus 4.9 months with biopsy, and median progression-free survival was 4.7 verses 2.5 months. The researchers reported that larger tumors were harder to ablate completely with LITT, but surprisingly, the amount of tumor ablated or left behind was not associated with survival. Patients whose functional status remained stable or improved after LITT tended to live longer.
While this study was not a comparison between LITT versus conventional resection surgery, it is worth noting the 14.9-month survival with LITT falls within the range typically reported in previous studies of open resection for butterfly gliomas (roughly 7-15 months).
While this was a small retrospective study, the results support further study of LITT as a minimally invasive option for selected patients with butterfly gliomas.
One of the biggest challenges after GBM treatment is figuring out whether a new or growing area on an MRI is real tumor growth or treatment effect such as pseudoprogression or radiation necrosis. Conventional MRI cannot reliably distinguish the two in a large portion of cases, often estimated at 30-40%.
Researchers assessed the literature to see how this problem is being addressed, including implementation of the RANO 2.0 guidelines. RANO (Response Assessment in Neuro-Oncology) is an international group that develops standardized guidelines for interpreting brain tumor scans, and its RANO 2.0 guidelines were published in 2023. Based on their review, the authors propose a tiered approach for distinguishing tumor growth from treatment effect: starting with RANO 2.0 MRI assessment, then move to advanced/perfusion MRI, then to amino-acid PET, then to biopsy when necessary. They emphasize that this is a potential framework, not yet a validated recommendation.
For patients, the practical takeaway is that when an MRI is unclear, there are increasingly more tools available to help determine what is really happening, including perfusion and amino-acid PET (and also fractional tumor burden mapping, which we've covered previously), but none can yet guarantee a definitive answer.
Researchers at the University of Michigan found that ZFTA-RELA fusion ependymoma (which make up most supratentorial ependymomas) tumor cells produce unusually high levels of itaconate, a substance normally made by immune cells. The tumor appears to use itaconate to help keep the ZFTA-RELA cancer-driving gene switched on, creating a cycle that helps the tumor grow. The researchers also found that the tumor changes the way it uses glutamine, a nutrient that helps provide the building blocks needed to make itaconate.
These discoveries have helped identify potential treatment targets. In mouse models, blocking either glutamine metabolism, the enzyme ACOD1 that makes itaconate, or related signaling pathways slowed tumor growth. Combining these treatments worked even better.
While this research is still preclinical, the University of Michigan team is now working with the Pediatric Neuro-Oncology Consortium (PNOC) to develop a clinical trial based on this research. We will keep an eye out and hope to see the trial open soon!
Registration is now open for the 5th Annual BrainStorm Summit, taking place September 16-18, 2026 in McLean, Virginia. The Summit brings together pediatric brain tumor families, researchers, clinicians, advocates, nonprofit organizations, and industry partners for three days of collaboration, education, research updates, and networking. With dedicated programming for children, teens, young adults, and adults, the event is designed to foster meaningful connections and advance progress against pediatric brain tumors. Learn more, register, and reserve discounted hotel accommodations at brainstormsummit.org.
This recent review article nicely summarizes the current state of glioblastoma treatment and emerging therapeutic strategies. While it does not present new clinical data, it comprehensively covers standard therapy, immunotherapy, precision medicine, novel drug delivery approaches, and new approaches to clinical trials.
We are proud to announce that a new, updated edition of our Brain Tumor Guide for the Newly Diagnosed is now available! You can view it online HERE or order a free printed copy HERE.
Our copay program has recently closed to new and renewal applications. We will reopen again when we are able to raise more funds. Of course, we will continue to pay claims for those who have an active grant. This program is funded entirely by donations earmarked for this purpose; if you'd like to make a donation towards this program, go to virtualtrials.org/donate and select 'Co-payment Assistance Fund' when you make a donation!
Preliminary Phase 2 results suggest that BPM31510, an investigational intravenous mitochondrial therapy, may improve outcomes in newly diagnosed glioblastoma (GBM) when added to standard radiation and temozolomide. BPM31510 is designed to deliver very high levels of oxidized CoQ10 into tissues, including the brain, where it may disrupt tumor metabolism, increase oxidative stress, and trigger cancer cell death. The treatment is given together with vitamin K1 to reduce coagulation-related side effects.
In this single-arm Phase 2 trial, BPM31510 was given with standard chemoradiation and temozolomide. Among 39 evaluable patients, median overall survival was 19.3 months. The most encouraging results were seen in the 24 patients with MGMT-unmethylated tumors, where median overall survival reached 29.3 months. It is not yet known whether or why MGMT-unmethylated patients appeared to benefit more, and these results need confirmation in larger randomized studies. Final results from all enrolled patients are expected later this year.
A Phase 1 trial from Children's National in Washington, DC tested an experimental autologous (patient-derived), non-genetically engineered T-cell therapy targeting WT1, PRAME, and survivin in children with aggressive brain tumors. The study enrolled 11 children with newly diagnosed DIPG and 22 with recurrent non-brainstem brain tumors who received the treatment. The therapy was generally well tolerated, but there was one potentially treatment-related death from tumor swelling in a child with DIPG, which led to a study protocol change. Median overall survival in the DIPG group was 13.7 months. Among the patients with recurrent non-brainstem tumors, three patients (14%) remain disease-free for 31.8-51.6 months without additional treatment, including one patient who had a complete MRI response. The three long-term survivors had recurrent medulloblastoma, anaplastic ependymoma, and high-grade glioma. While this study was designed mainly to assess safety rather than efficacy, the results support further investigation of this personalized T-cell approach.
Researchers at Northwestern have identified a biological pathway that may help explain why some glioblastoma (GBM) patients respond to immunotherapy while many do not. Using CRISPR-based screening in mouse models, they found that activation of the MAPK/RAF-MEK-ERK signaling pathway made tumors more recognizable to the immune system and improved responses to immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 therapies.
The findings build on earlier observations that rare BRAF and PTPN11 mutations, which activate MAPK signaling, were more common among the small number of GBM patients who had exceptional responses to immunotherapy. The researchers found that MAPK/ERK activation increases inflammatory signals, promotes T-cell infiltration into tumors, and may help immune cells recognize and attack cancer cells.
The team cautions that MAPK activation is necessary but not sufficient for immunotherapy response; in other words, some patients with this pathway activation still do not respond. If validated in human studies, MAPK/ERK activity could become a biomarker to help identify which GBM patients are most likely to benefit from immunotherapies.
