RESEARCH NEWS FOR THE THIRD BIMESTER OF 2025

Although published somewhat late, this is the thirty-second article in the project, which aims to periodically (every two months) collect research updates on potential treatments for glioblastoma multiforme. Below, we list the news items we consider most significant that have emerged in the last two months. As with previous articles in the series, each news item will be preceded by the original title with a link to the source and followed by a brief commentary. The criteria for selecting news items is always to generally include only news related to clinical-stage research, unless the potential of the research for the treatment of glioblastoma is truly significant.

A phase 1 safety and feasibility trial of a ketogenic diet plus standard of care for patients with recently diagnosed glioblastoma
The ketogenic diet (KD) is a specific dietary regimen, very low in carbohydrates and high in fat, with the aim of inducing the production of ketones. Ketones are then used as an alternative source of energy by the body. Using the ketogenic diet as part of cancer treatment is attractive because tumor cells are unable to utilize ketones as an energy source and are therefore “starved” of energy. This clinical study demonstrates that the ketogenic diet is both feasible and safe. Seventeen of the 21 participants with newly diagnosed glioblastoma were able to maintain the ketogenic diet for at least four weeks, and 12 completed the full 16-week course. Ten of the 12 participants continued the ketogenic diet after the study concluded. According to the researchers, the diet was well tolerated, although the most common symptoms were mild loss of appetite, flu-like symptoms, diarrhea, and fatigue. No participants discontinued the study due to side effects. Quality of life and cognitive function measures were stable and, in some cases, improved, but statistical analysis was not possible due to the small number of subjects. Progression-free survival and overall survival were also favorable, but statistical analysis was not possible. This study provided preliminary data for an ongoing Phase 2 randomized clinical trial (NCT05708352), which will compare the ketogenic diet with preliminary standard dietary recommendations, both combined with standard therapy, in patients newly diagnosed with glioblastoma.

A cross-talk established by tumor-targeted cytokines rescues CAR T cell activity and engages host T cells against glioblastoma in mice
A recent article published in Science Translational Medicine identifies a new approach to increase the efficacy of CAR T (chimeric antigen receptor T-cell) therapies in glioblastoma. This new method uses modified macrophages, a type of white blood cell, administered simultaneously with CAR T cells to modify the tumor’s environment. The macrophages release cytokines onto the tumor surface, thus making the CAR T cells more effective once they penetrate the tumor cells. The end result is the activation of immune responses within the tumor, rather than systemically, with the potential not only to increase efficacy but also to reduce side effects. The first human clinical trial incorporating this approach, called TEM-GBM (NCT03866109), is underway in Italy. It is evaluating the safety of modified macrophages, called Temferon, administered alone.

Gabapentin Linked to Longer Survival in Glioblastoma Brain Cancer
A new study suggests that postoperative gabapentin, a neuromodulator commonly used for neuropathic pain, may improve overall survival in patients with newly diagnosed glioblastoma. In two cohorts totaling 1,072 patients, those who received gabapentin lived an average of four months longer at Mass General Brigham and six months longer at UCSF than those who did not. Gabapentin targets TSP-1, a synaptogenic protein implicated in tumor progression. It is important to note that the study results showed an association between gabapentin use and a reduction in serum TSP-1 levels. The study has some limitations, including its retrospective design and dosing variability among patients, but it is hoped that future prospective trials will confirm these results and define the optimal dosage.

Targeting the clock: new drug disrupts glioblastoma stem cells
A team of researchers has developed SHP1705, a compound capable of targeting glioblastoma stem cells (GSCs) by affecting their circadian rhythm, an internal mechanism these cells exploit to survive and proliferate. We know how cells Glioblastoma stem cells are the main culprits of recurrence and drug resistance. GSCs manipulate the biological clock protein CRY2; SHP1705 restores its activity, interrupting the vital processes of tumor cells. This compound reduces GSC viability without harming healthy brain cells. It has also been demonstrated to be effective on both chemotherapy-sensitive and chemotherapy-resistant tumor lines and to slow tumor growth in mouse models. The compound SHP1705 successfully completed a Phase 1 study in healthy volunteers, demonstrating a good tolerability profile (mild side effects such as nausea and headache). This approach opens a new therapeutic avenue, targeting a specific vulnerability of glioblastoma, with the potential to increase selectivity and efficacy while reducing systemic side effects.

Dual-Target CAR T-Cell Therapy Slows Glioblastoma Growth
CAR T-cell therapy for recurrent glioblastoma (GBM) received much attention last year after early studies showed tumor shrinkage. Many experts in the field, however, remained cautious, as responses tended to be temporary. New results from a phase 1, dose-escalation study conducted at the University of Pennsylvania on patients with recurrent GBM are helping clarify the potential of this therapy. Using dual-target CAR T cells, designed to target two proteins present on GBM cells (EGFR and IL-13Ra2), researchers observed tumor shrinkage in 62% of patients (8 out of 13) who still had visible disease after surgery. Survival data for all patients treated so far (n=18) are still being collected, but several study participants have lived 12 months or more after treatment, and one patient has maintained stable disease for over 16 months. The initial cohorts of this study received a single infusion of CAR T cells, but more than one infusion is planned in the future. Studies are also planned to evaluate this treatment in patients with newly diagnosed GBM.

Phase II propensity-matched controlled trial evaluating metformin as an adjunct to neoadjuvant, concomitant, and adjuvant temozolomide and hypofractionated accelerated radiotherapy (M-HART) in glioblastoma patients (NCT02780024)
A study recently presented at the ASCO meeting suggests that a new protocol, involving the addition of metformin, may improve outcomes in patients with newly diagnosed glioblastoma. In this Phase II study conducted in Canada, 50 patients received metformin along with temozolomide (TMZ) before surgery, during an accelerated radiotherapy regimen (60 Gy over 4 weeks), and for 6 cycles of maintenance chemotherapy. These patients were compared with 50 matched patients who had received the standard Stupp protocol. The experimental group showed a significantly longer median survival (24.1 months versus 17.7 months in the standard-care group) and improved progression-free survival (13.7 months versus 11.0 months). This finding was particularly notable in patients with methylated MGMT tumors who had undergone total resection: in this subgroup, median survival reached 41.9 months compared to 17.8 months in the control group.

Molecular Correlates of Long-Term Response to Bevacizumab in Glioblastoma
A study published in JCO Precision Oncology (June 2025) analyzed over 3,100 glioblastoma tumor samples, 571 of which were treated with bevacizumab, to identify biomarkers that could predict which patients would benefit most from this drug. The results tell us that the overall median survival of patients treated with bevacizumab was 17.5 months. In patients who received bevacizumab for at least 1 year, the median survival increased to 33.8 months, compared to 15 months in those who received it for less than 6 months. Those who benefited from bevacizumab for a prolonged period (≥1 year) showed a higher incidence of: LRIG3 amplification (9% vs 1%), CDK4 amplification (22% vs 8%), DDIT3 amplification (14% vs 4%), SETD2 mutations (10% vs 3%), MGMT promoter methylation (66% vs 32%). In contrast, EGFR amplification was more common among those who received bevacizumab for a short period (≤6 months) (46% vs 20%). These data suggest that CDK4 amplification may help identify glioblastoma patients who may benefit from bevacizumab in the long term, while EGFR amplification may indicate a more limited response. This approach promises to refine patient selection and optimize the clinical use of bevacizumab.

Phase 2B Trial for Cancer Vaccine in Newly Diagnosed Glioblastoma Will Continue
The SURVIVE study (Phase 2b), evaluating the immunotherapy vaccine SurVaxM in patients with newly diagnosed glioblastoma, will continue according to the original protocol: the independent safety monitoring committee concluded that interim data do not require any modification to the study. SurVaxM is a peptide-based vaccine that stimulates the immune system to recognize and attack tumor cells expressing the protein survivin. It is administered intravenously after surgery and radiation therapy: initially with four injections spread over six weeks, followed by maintenance doses every three months. The study is ongoing at multiple centers and involves approximately 247 patients divided into two arms: experimental treatment (SurVaxM + standard therapy) and placebo + standard therapy. The primary objective is to evaluate overall survival (OS); Secondary outcomes include progression-free survival (PFS), tumor response rate, and safety. The vaccine has already demonstrated a good safety and tolerability profile, which is essential for maintaining patients’ quality of life. Confirmation of the continuation of the SURVIVE trial without modifications is a positive sign: the SurVaxM vaccine continues to emerge as a potential innovative therapeutic strategy, worth evaluating for its potential to improve survival in patients with newly diagnosed glioblastoma.

Thanks to those who have helped and continue to help us keep the volunteer organization alive and develop our projects, always focused on supporting patients and their caregivers. The call for applications for the “Hope and Courage” project has closed, and during the month of August, we will publish the list of candidates selected for specialist training. That’s all for this issue of research news. Best of luck to all those fighting glioblastoma and their loved ones!