Research News in the First Two-Months of 2025
This is the thirtieth article of the project that aims to periodically collect (every two months) the research news on possible treatments for glioblastoma multiforme. Below I list the news that we considered most significant that emerged in the last two months. As with the 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 comment. The criterion with which the news items are chosen is always to generally include only news related to research in the clinical phase, unless the potential of research for the treatment of glioblastoma is truly remarkable.
Temozolomide chemotherapy for patients with newly diagnosed glioblastoma in the CENTRIC EORTC 26071-22072 and CORE trials: does time of administration matter
This study compared the efficacy and toxicity of morning versus evening temozolomide (TMZ) chemotherapy in patients with newly diagnosed glioblastoma. Post hoc analysis found no significant differences in clinical outcomes based on the time of TMZ administration. However, bone marrow toxicity was noted to be influenced by the time of administration, suggesting that further studies are needed to determine the optimal time to reduce side effects.
Treatment strategy reprograms brain cancer cells, halting tumor growth
UCLA researchers have developed a new treatment strategy for glioblastoma, combining radiation therapy with the plant-derived compound forskolin. This combination induces tumor cells into a dormant state, preventing them from dividing and spreading. In tests on mice, adding forskolin to radiation therapy prolonged survival, offering a potential new way to fight glioblastoma. Radiation therapy kills many tumor cells, but temporarily makes glioma stem cells more flexible, providing the opportunity to alter their identity. The researchers exploited this flexibility by using forskolin to push these cells into a non-proliferative state, similar to neurons or microglia. Forskolin was able to cross the blood-brain barrier, significantly reducing glioma stem cells and slowing tumor proliferation. This discovery represents a novel approach to treating glioblastoma, aimed at reprogramming aggressive tumor cells into harmless cells. Further clinical studies will be needed to confirm the efficacy of this therapeutic combination in humans.
Plus Therapeutics Announces Peer-Reviewed Publication in Nature Communications Highlighting Promising Phase 1 Results for Rhenium (186Re) Obisbemeda in Glioblastoma
Plus Therapeutics ha annunciato la pubblicazione peer-reviewed dei risultati di Fase 1 per il Rhenium (^186Re) obisbemeda nel Plus Therapeutics announced the peer-reviewed publication of Phase 1 results for Rhenium (^186Re) obisbemeda in the treatment of relapsed malignant glioma in Nature Communications. The study enrolled 22 patients, demonstrating that the treatment was well tolerated, with adverse events primarily grade 1 or 2. The median overall survival was 15 months, with a median progression-free survival of 2.8 months. These results support further clinical development of Rhenium (^186Re) obisbemeda for malignant brain tumors.
Short-course hypofractionated proton beam therapy, incorporating ^18F-DOPA PET and contrast-enhanced MRI targeting, for patients aged 65 years and older with newly diagnosed glioblastoma: a single-arm phase 2 trial
A phase 2 study evaluated the efficacy of hypofractionated proton beam radiation therapy guided by ^18F-DOPA PET in patients aged 65 years and older with newly diagnosed glioblastoma. Results showed a median survival of 13.1 months, with 56% of participants alive at 12 months, exceeding historical data indicating a median survival of 6 to 9 months. The therapy was well tolerated, with no grade 4 or 5 toxicities. These results prompted the initiation of a randomized phase 2 study to compare this regimen to standard of care.
Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma
This study documented the first use of a neoadjuvant triplet immunotherapy (PD-1, CTLA-4, and LAG-3 inhibitors) in a patient with newly diagnosed glioblastoma. The combination administered before surgery increased the infiltration and activation of immune cells within the tumor. At the time of publication, the patient showed no signs of recurrence beyond 18 months. These pioneering results led to the organization of a clinical trial to evaluate its safety and efficacy in a larger number of patients.
Programs, origins and immunomodulatory functions of myeloid cells in glioma
These researchers analyzed approximately 200,000 immune cells from glioma samples, identifying four gene expression “programs” that regulate immune activity in the tumor microenvironment. The study shows that some gene programs suppress the immune response while others activate it. For example, the use of dexamethasone in patients was associated with an immunosuppressive program that could reduce the effectiveness of immunotherapies. These findings provide a molecular roadmap for developing strategies to modulate the immune response and enhance the effectiveness of immunotherapy in glioblastoma.
Molecular and cellular dynamics of the developing human neocortex
This study mapped gene expression in human brain cells during development, revealing the existence of a new type of neural stem cell. This cell, active in the first decades of life, seems capable of giving rise to glioblastoma tumor cells in adulthood. The discovery suggests that glioblastomas exploit genetic programs of brain development to grow aggressively, paving the way for targeted therapies that interrupt these mechanisms underlying tumorigenesis.
Sonodynamic therapy with a single neoadjuvant, diffuse delivery of low-intensity ultrasound with 5-ALA in treatment-naïve glioblastoma results in tumor-specific cytotoxic edema and increased apoptosis
A preliminary clinical study tested Sonodynamic Therapy (SDT), which combines low-intensity ultrasound with 5-ALA, in three patients with glioblastoma who were not candidates for total resection. After a single administration, SDT induced tumor cell death without damaging healthy brain tissue and without significant adverse effects. This non-invasive therapy suggests an innovative approach to target brain tumors in a diffuse manner and will be evaluated in a randomized clinical trial later this year.
Paxalisib shows overall survival benefit in GBM (GBM-AGILE trial) and FDA feedback on approval pathway
In the adaptive phase 2/3 GBM-AGILE study for glioblastoma, the investigational drug paxalisib (PI3K inhibitor) showed an improvement in overall survival in patients with newly diagnosed GBM and an unmethylated MGMT promoter compared to standard therapy. In light of these data, the FDA communicated that, although paxalisib does not qualify for accelerated approval, the evidence of efficacy on survival could support a standard approval. The regulatory body has agreed with the company on the design of a registrational phase 3 study necessary for eventual final approval.
Functional reprogramming of neutrophils within the brain tumor microenvironment by hypoxia-driven histone lactylation
Scientists have discovered a new mechanism by which glioblastomas reprogram infiltrating neutrophils, transforming them from anti-cancer cells to cells that promote tumor growth. The study reveals that under conditions of intra-tumor hypoxia, neutrophils acquire high levels of ARG1, a gene that suppresses the anti-tumor immune response. Blocking this epigenetic metabolic pathway could prevent neutrophils from supporting the tumor, offering a new target to enhance the effectiveness of immunotherapy in glioblastoma.
Un grazie a quanti ci hanno aiutato e continuano ad aiutarci a manterere viva l’organizzazione di volontariato e a sviluppare i nostri progetti sempre centrati sul supporto ai pazienti, ai loro caregiver. Questo è tutto per questo numero sulle novità della ricerca. Prima di chiudere vi annuncio che in questi giorni abbiamo attivato in via sperimentale anche un profilo Instagram dove pubblicheremo alcuni brevi video informativi sul glioblastoma. Un in bocca al lupo di cuore e un Buon 2025, pieno di speranza, a tutti coloro che stanno combattendo contro il glioblastoma e ai loro cari!
