RESEARCH NEWS FOR THE FIFTH BIMESTER OF 2025

This is the thirty-fourth article in the project, which aims to periodically (every two months) collect research news 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 for research in the treatment of glioblastoma is truly significant.

Dispersed Glioblastoma Cells Prove More Aggressive
A recent study published in Cancer Cell reveals a potentially key mechanism in the resistance and recurrence of Glioblastoma multiforme (GBM): tumor cells that disperse from cell clusters form a more aggressive and treatment-resistant population. Specifically, researchers at Sylvester Comprehensive Cancer Center, led by Dr. Anna Lasorella and Dr. Antonio Iavarone, used a spatial transcriptomics approach on the CosMx platform to map cellular gene expression within the tumors of GBM patients. They observed that, while some cells remain aggregated in well-defined clusters, another “dispersed” population detaches and occupies mixed areas of the tumor tissue—these dispersed cells show reduced expression of cell adhesion molecules and increased expression of genes related to plasticity. Clinical significance: Plasticity, or the ability of tumor cells to change their identity and behavior, is correlated with resistance to radiation and chemotherapy and worse patient outcomes. The authors hypothesize that standard therapies may, in some cases, promote cell dispersion and thus worsen the disease. Implications for patients and caregivers: This discovery opens a new line of research—the idea is that keeping cells “aggregated” may limit plasticity and slow tumor progression. Although there are no immediate practical clinical applications yet, the study suggests that biomarkers based on the proportion of dispersed vs. aggregated cells could be developed in the future, and perhaps new treatments aimed at strengthening the bonds between tumor cells to make them less aggressive.

Guiding Principles for Adult CNS Tumor Treatment Programs
This study emphasizes how the complexity and interdisciplinary nature of brain tumors require a structured care model: multidisciplinary teams that include neurosurgeons, oncologists, radiologists, neuropsychologists, and support specialists. The importance of standardized protocols, continuous monitoring of clinical data, networks for sharing best practices, and the integration of clinical and translational research is highlighted. Furthermore, the article emphasizes the quality of facilities and the center’s experience in treatment—factors associated with better outcomes for patients with brain tumors.
For patients and caregivers, this means that choosing a treatment center can make a difference: choosing programs that adhere to these principles can increase their chances of accessing cutting-edge treatments and comprehensive support.
The seven guiding principles identified by the authors define what should characterize a truly specialized center for adult central nervous system tumors.
First, a dedicated program is needed—a specific facility focused exclusively on CNS tumors, with targeted expertise and experience.
Second, the center must treat an adequate volume of patients each year: a sufficient number of cases guarantees clinical experience and quality of care.
Third, a stable multidisciplinary team composed of neurosurgeons, oncologists, radiation oncologists, neuroradiologists, specialized nurses, and other professionals dedicated to brain tumors is needed.
Fourth, advanced molecular tests must be available, essential for accurate diagnosis according to WHO standards and for guiding the most modern therapies.
Fifth, the center must offer access to specific clinical trials or actively collaborate with institutions that make them available.
Sixth, a multidisciplinary tumor board is required, which meets regularly to discuss cases and define the best treatment path.
Seventh, the program must guarantee comprehensive support services for patients and caregivers: rehabilitation, neuropsychological support, social assistance, palliative care, and dedicated information resources.

Biomarker Analysis Reveals Clues to Long-Term Survival in Glioblastoma Patients Treated with SurVaxM
A recent analysis conducted by Roswell Park Comprehensive Cancer Center has identified several tumor biomarkers that may explain why some patients with glioblastoma multiforme (GBM) respond particularly favorably to the immunotherapy vaccine SurVaxM, administered alongside standard therapies. The study involved patients with newly diagnosed GBM treated with surgery, chemoradiation, and then SurVaxM. Researchers analyzed the molecular profile of the tumor before treatment in 34 of 63 patients participating in the phase 2 study using exome sequencing and RNA-seq. They compared the tumors of patients with short survival (less than 18 months) to those who lived longer (more than 18 months). The main findings: “Long-term survivors” showed high infiltration of B and T cells (key components of the immune system) and more marked activation of genes related to interferon-γ and interferon-α, signals indicating a more active immune response in the tumor microenvironment. Furthermore, a five-gene expression profile was identified that, along with a B-cell-specific signature, predicted survival only in patients treated with SurVaxM (and not in a control group without immunotherapy), suggesting that these biomarkers are specific to vaccine response, not just general indicators of prognosis. Finally, the study highlights that 10 patients achieved survival of more than seven years, including a group of five still without recurrence.
In summary, at least for SurVaxM, it seems possible to predict which treatment will work best. This type of study should be conducted for each type of treatment in order to maximize efficacy on the patient’s specific glioblastoma and move closer to what should be a personalized therapy for the patient’s specific tumor.

Sonodynamic Therapy Using 5-Aminolevulinic Acid for Malignant Gliomas: A Review
This article also reviews the few, but important, clinical studies conducted to date on sonodynamic therapy (SDT) with 5-ALA in malignant gliomas. These are primarily small pilot studies in Japan, specifically aimed at patients with relapse. The results show that the procedure is feasible and generally well tolerated, with no serious side effects attributable to the treatment. In some cases, temporary stabilization of the disease has been observed, but the numbers are too small to draw conclusions about its efficacy. The authors emphasize that, despite these initial encouraging signs, phase II or III clinical studies are completely lacking, and there are no controlled trials demonstrating a concrete survival benefit. SDT with 5-ALA therefore remains a promising but still highly experimental technology, awaiting larger and more rigorous clinical trials.

Glioblastoma treatment combo shows promise in pilot study
A small pilot study has evaluated a new therapeutic combination for relapsed glioblastoma, achieving very encouraging preliminary results in a clinical setting where options are extremely limited. The therapy combines nogapendekin alpha-inbakicept, an agent that stimulates T and NK cells, with the Optune Gio device, based on electrical fields (TTFields). The study involved only five patients, all of whom had previously been treated with standard treatments and were progressing. Despite this, all showed clinical benefit: three patients experienced significant tumor shrinkage (in two cases almost complete), while the other two maintained stable disease. Furthermore, an increase in circulating immune cells was observed during treatment, a sign that the combination could effectively enhance the immune response against the tumor. These are encouraging but still very preliminary results: the number of patients is small and the study is not randomized. However, they indicate that the combination of immunotherapy and electrical fields could represent a potential research avenue for patients with relapsed glioblastoma. Larger clinical studies are needed to confirm its efficacy.

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.
Regarding the “Speranza e Coraggio” project, as you may have read, the free psychological support service has begun, and several patients and caregivers have begun using it. To do so, simply register at navigator.glioblastomamultiforme.it, select the calendar, select “Psycho-oncology / Neuropsychology” as specialty, choose one of the listed specialists, and then select one of the available appointments. Navigator will send you instructions with the link to access the video conference.
That’s all for this issue of research news. Best of luck to all those fighting glioblastoma and their loved ones!