The annual Tumor Takedown fundraiser is coming up this Saturday, May 2nd from 4-7pm at Millennial Brewing Company in Fort Myers, Florida. This event is put on by Zachary, brain tumor survivor and thriver, to raise local awareness of brain cancer. 100% of the donations go to the Musella Foundation to help brain tumor patients through emotional and financial support, education, advocacy and raising money for brain tumor research. For more info, click here! 

The phase 2/3 GBM AGILE platform trial has now reported final results for the regorafenib (Stivarga) arm. In the study, regorafenib was tested in both recurrent glioblastoma (against lomustine) and newly diagnosed unmethylated glioblastoma (against standard chemoradiation). The trial did not find an overall survival benefit in either group, and regorafenib was associated with more toxicity compared to control. These findings are not entirely surprising given the modest survival signal seen in the earlier phase 2 REGOMA trial for recurrent GBM.

While disappointing, the GBM AGILE platform continues to represent an important advance in GBM drug development by enabling rapid, randomized testing of drug candidates within an adaptive framework, allowing ineffective agents to be deprioritized more efficiently.

From a broader perspective, these results also reinforce a recurring theme in GBM: monotherapy approaches, particularly with targeted kinase inhibitors, have repeatedly failed to translate early-phase signals into durable clinical benefit. This underscores the need for rational combination strategies that address the multiple redundant resistance pathways that drive GBM progression.

A new study has identified miR-181d, a naturally occurring microRNA that regulates gene expression, as a potential mediator of glioblastoma (GBM) treatment sensitivity. The study team found that higher miR-181d levels were associated with GBM “exceptional responders,” the rare patients who experience unusually durable responses to therapy.

The data suggest miR-181d improves treatment response by suppressing multiple resistance pathways. Prior work showed miR-181d suppresses MGMT, a key mediator of temozolomide resistance. In this study, the authors show that miR-181d also suppresses RAD51, a critical DNA repair protein, thereby increasing tumor sensitivity to radiation and other DNA-damage therapy. Lower RAD51 expression in patient tumors was associated with longer survival, consistent with prior reports.

In preclinical models, intracranial delivery of miR-181d prior to radiation improved tumor control and survival. In an immunocompetent recurrent GBM mouse model, median survival increased from 41 days with radiation alone to 58 days with the addition of miR-181d, with roughly half of treated animals surviving beyond three months. Re-implantation of GBM cells into long-term survivors resulted in lower tumor burden by bioluminescence imaging, consistent with durable anti-tumor immune recognition.

These findings support the concept that miR-181d may both enhance tumor sensitivity to standard therapy and help sustain anti-tumor immunity. The authors are now working toward a clinical trial evaluating local delivery of miR-181d during surgery.

This UCSF preclinical study reaffirms IL-6 as an important regulator of the glioblastoma (GBM) immune tumor microenvironment (TME) and a potential target for combination therapy. Using integrated spatial and single-cell analyses of patient-matched human GBM samples, the authors show that lower baseline IL-6 is associated with the rare clinical responses seen with immune checkpoint inhibitors (ICIs), while higher IL-6 correlates with poorer outcomes. These findings are consistent with prior observations by Dr. Steven Brem and others linking IL-6 to glioma progression, senescence-associated genes, immune suppression and prognosis in GBM.

In the current study by Jacob Young, et al., using preclinical models, IL-6 blockade alone was not sufficient for durable tumor control, but it shifted the tumor immune microenvironment to a more immunoresponsive TME by reducing regulatory T cells, activating dendritic cells, and increasing antigen presentation and effector CD8+ T-cell activity. When combined with immune checkpoint inhibition and radiotherapy, IL-6 blockade translated into more durable anti-tumor responses. This work further supports a combination strategy of targeting cytokine-driven resistance pathways by blocking IL-6, and potentially other immunosuppressive cytokines, to overcome immunotherapy resistance in GBM. Currently, an NRG multicenter trial (NCT04729959), combining anti-IL6R antibody (tocilizumab) with an ICI (atezolizumab) and fractionated radiotherapy has completed accrual and the data is being analyzed. We will share those results when they become available! 

A recent publication in Springer Nature reports preclinical results for an experimental gene therapy developed by the Scottish company Trogenix for glioblastoma (GBM). The therapy uses engineered DNA elements called Synthetic Super-Enhancers (SSEs), delivered via adeno-associated virus (AAV) vectors. The SSEs are designed to activate specifically in GBM stem-like cells by exploiting SOX2-driven transcriptional programs. Once activated, they deliver two payloads: HSV-TK for targeted tumor cell killing via a prodrug mechanism, and IL-12 to stimulate an anti-tumor immune response.

The approach was first validated in patient-derived GBM stem cell cultures, where SSE activity was seen in tumor cells but not in non-tumor neural cells. It was then tested in orthotopic, immunocompetent mouse models of GBM. In these models, a single dose led to rapid tumor regression within 1-2 weeks, with complete tumor clearance in 83% of treated animals. No tumor recurrence or significant toxicity was observed over 11 months, and re-challenged mice did not develop new tumors, suggesting a durable immune response.

A first-in-human Phase I/II GBM trial is planned for 2026.

This article highlights growing interest in wearable devices to monitor brain health, including seizure detection. Current wearables may be helpful for brain tumor patients who experience tonic-clonic seizures, as they can alert a caregiver remotely during an event. However, they do not reliably detect focal seizures, which limits their usefulness for many patients with brain tumor-related epilepsy.

GBM AGILE is a large, international Phase 2/3 trial for newly diagnosed and recurrent glioblastoma. It has an innovative adaptive design that allows multiple experimental therapies to be tested at the same time against a shared control arm to more efficiently identify promising treatments. We have a Musella Foundation recorded webinar about the trial available HERE.

GBM AGILE is now adding a new study arm for Tinostamustine, an investigational drug that combines DNA-alkylating activity (to damage tumor DNA and trigger cell death) with HDAC inhibition (an epigenetic mechanism that may increase tumor sensitivity and immune recognition). Earlier phase 1 studies showed the drug has a manageable safety profile.

We are proud to announce that we have awarded a new $50,000 venture philanthropy grant to AVIL Therapeutics to support promising research aimed at developing a targeted therapy for glioblastoma (GBM). Our venture philanthropy model helps accelerate research projects that show both scientific rigor and clear potential for patient benefit. By supporting early-stage but transformative ideas, we help bridge the gap between discovery and future clinical trials. 

This grant supports preclinical work focused on AVIL (advillin), a newly identified cancer driver that appears to play a critical role in glioblastoma growth and survival, while being largely absent from normal brain tissue. Specifically, the funded research will focus on advancing preclinical validation and lead optimization, with the goal of generating the data needed to support future clinical development. By emphasizing rigorous science and translational relevance, this work aligns closely with our mission to accelerate progress toward more effective treatments for patients and families affected by GBM. 

We are also very proud to announce the award of a $50,000 venture philanthropy grant to KiraGen Bio to support groundbreaking work in engineered CAR-T cell therapy for glioblastoma (GBM). KiraGen is developing off-the-shelf CAR-T cell therapies that are engineered to 'tune out' immune suppressive signals in the tumor microenvironment, thus helping the CAR-T treatment remain active and effective longer without increasing toxicity. 

This grant will support a study to determine which of KiraGen’s lead 6-knockout allogeneic CAR-T variants delivers the most durable anti-tumor function when faced with realistic GBM tumor microenvironment suppression. Using patient-derived GBM tumoroids that preserve native tumor architecture and immune suppressive signaling, the research team will test these engineered cells against conventional CAR-T to decide which configuration is best positioned to advance toward a clinical trial. By supporting this work, we hope to move the next generation of engineered cell therapies closer to patients and families affected by GBM.

The FDA has granted breakthrough therapy designation to plixorafenib, an oral targeted drug, for patients with recurrent high-grade gliomas with a BRAF V600E mutation. This designation allows closer collaboration with the FDA and is intended to shorten development time.

Early clinical results show encouraging activity, particularly in brain tumors. In a small predefined subgroup of 9 patients with BRAF V600E-mutated primary CNS tumors (including high-grade gliomas) who had not received prior similar targeted therapies, 67% had tumor shrinkage and more than 75% experienced clinical benefit (shrinkage or stable disease).

Across all BRAF V600-mutated solid tumors, the response rate was 42%, with a median response duration of 17.8 months and over 70% experiencing clinical benefit.

The drug has shown a generally favorable safety profile, and an ongoing phase 2 trial is further evaluating its effectiveness in BRAF-mutated cancers, including brain tumors. While these results are promising, larger studies are needed to confirm efficacy and response durability in high-grade glioma.

Researchers have been working to overcome a major limitation in glioblastoma research: traditional lab models don’t accurately reflect how tumor cells infiltrate the human brain. At institutions such as Weill Cornell and others worldwide, scientists are now using patient-derived brain organoids (three-dimensional lab ‘mini-brains’ grown from a patient’s own tumor cells) to study tumor behavior and test hundreds of existing drugs or combinations in a personalized way. These organoid platforms can better mimic each patient’s tumor genetics, microenvironment, and patterns of invasion, and are showing promise for identifying therapies that might be more effective than standard treatments alone. While this technology has not yet been used in the US to guide therapy in large clinical trials, several research centers are actively developing organoid screening systems and working with regulatory agencies to design early-phase studies. We hope that, in coming years, organoid-based drug testing could help tailor treatments to individual patients and accelerate development of new therapies for high-grade brain cancers.

The National Institute for Health and Care Excellence (NICE) has published final guidance approving vorasidenib (brand name Voranigo) for prescription on the NHS in England and Wales for people aged 12 and older with IDH-mutant low-grade gliomas, including astrocytoma and oligodendroglioma. The treatment will be made available through the Cancer Drugs Fund, offering faster access while routine NHS funding is established.

Vorasidenib, which received MHRA marketing authorization in October 2025, was shown in the INDIGO trial to slow tumor growth and delay the need for chemotherapy or radiotherapy, helping patients maintain quality of life for longer. NICE’s positive recommendation reflects both the clinical evidence and the strong support from patients, families, and charities advocating for access to this much-needed therapy. This is only the second new NHS-approved drug for brain tumors since temozolomide in 2006, marking a meaningful step forward for patients and families affected by low-grade gliomas.

This is a nice review article summarizing recent advances in immunotherapies for glioblastoma, including leading strategies to overcome treatment resistance and the immunosuppressive tumor microenvironment. One of the authors, Dr. Michael Lim, is a 2026 Musella Foundation grant recipient!

Great to see Forbes covering the Phase 2 sonodynamic therapy trial for newly diagnosed glioblastoma; our recorded webinar with more details is available HERE. 

The current World Health Organization (WHO) brain tumor classifications already incorporate one molecular feature (CDKN2A/B homozygous deletion) that can upgrade an IDH-mutant astrocytoma to grade 4, even in the absence of classic high-grade histologic features. However, this new study shows there are several additional molecular alterations that independently predict worse survival in IDH-mutant astrocytoma and therefore may warrant inclusion in grading criteria.

Across two large cohorts of roughly 1,200 patients, the authors found that CDK4 amplification, CCND2 amplification, PDGFRA alterations, PIK3R1 mutations, MYCN amplification, and EGFR alterations are all associated with significantly poorer outcomes in IDH- mutant astrocytoma. This is important, because roughly 18% of tumors currently classified as grade 2 or 3 harbor at least one of these high-risk molecular features.

Clinically, these tumors fall into an intermediate-risk category, with survival outcomes worse than standard grade 2 or 3 tumors but still better than grade 4 disease. Median overall survival in this group was approximately 67 to 82 months, compared to 135 to 141 months for typical grade 2 or 3 tumors and 35 to 45 months for grade 4 tumors. 

For patients, the key implication is that a tumor labeled as grade 2 or 3 may still behave more aggressively if these molecular features are present. For clinicians, the findings support consideration of expanding molecular grading criteria to include these additional alterations, as they provide independent prognostic value, help identify patients who may benefit from closer monitoring or more aggressive upfront treatment, and improve risk stratification for clinical trials.

Hoops for Hannah is a March Madness bracket contest that raises funds for brain tumor research in memory of Hannah Taylor.  Participants have donated over $90,000 to brain tumor research through Hoops For Hannah since Hannah's passing in 2012. This cause is worth fighting for!

There is no entry fee, as Hannah's family generously provides a $1,000 First Prize; donations to Brain Tumor Research are not required but gratefully accepted. 100% of all donations go to the Musella Foundation! For details to enter, click here.

The Musella Foundation is working on an updated edition of our Brain Tumor Guide for the Newly Diagnosed. The final chapter, titled "Hope for the Future," will live on our website so that it can be updated regularly. To read it, click here!   

A new study shows adding berzosertib (an ATR inhibitor) to radiation appears to make H3K27-altered diffuse midline glioma more sensitive to treatment by blocking tumor DNA repair, leading to greater tumor cell death in preclinical models. This suggests a promising strategy to enhance radiotherapy effectiveness, but it remains experimental and requires clinical trials to confirm safety and benefit for patients.

In this Northwestern study, researchers found that glioblastoma (GBM) tumors 'hijack' microglia metabolism by exploiting a fructose transporter called GLUT5, causing the microglia (the brain's resident immune cells) to take up and metabolize fructose in a way that suppresses anti-tumor immunity. To test its role, they used genetically engineered mice lacking GLUT5.

In multiple mouse GBM models, GLUT5-deficient mice showed significantly reduced tumor growth and improved survival, indicating this pathway is required for tumor progression. The microglia became more inflammatory and less immunosuppressive, and there was greater activation of a broader immune response, including increased antigen presentation, higher inflammatory signaling, and shifts toward more active T cell responses (including CD8+ T cells).