RESEARCH NEWS IN THE FOURTH BIMESTER OF 2025

This is the thirty-third article in the project, which aims to periodically (every two months) collect research news on potential treatments for glioblastoma multiforme. Below, we list the most significant news items 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 into the treatment of glioblastoma is truly significant.

A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen
A group of researchers is proposing the AVRO regimen, a new adjuvant approach for the treatment of glioblastoma that uses four drugs already approved for other uses: aprepitant, vortioxetine, roflumilast, and olanzapine. The idea is to leverage drug repurposing to target various mechanisms involved in tumor growth—inflammation, neurotransmitter signaling, proliferation, and response to cellular damage—while simultaneously improving symptoms that impair quality of life, such as nausea, loss of appetite, and sleep disturbances.
The authors emphasize that, although the evidence is currently primarily preclinical, the drugs’ safety and availability make it attractive to initiate Phase II clinical trials to verify their efficacy as a complement to standard therapies.
This approach is very similar to the CUSP9v3 protocol, which, however, has not yet begun due to the failure to raise sufficient funding to initiate a subsequent phase clinical trial.

Bevacizumab alternating chemotherapy for improving the survival of patients with recurrent high-grade glioma
A retrospective study of 95 adult patients with recurrent high-grade glioma compared the use of bevacizumab in combination with alternating chemotherapy (BAC) versus bevacizumab alone. The results show a significant improvement in overall and post-relapse survival in the BAC group, with a particularly pronounced effect in patients with MGMT promoter methylation. The authors conclude that the addition of alternating chemotherapy may be a useful option for prolonging survival in patients ineligible for clinical trials, while emphasizing the need for confirmation in prospective, randomized studies. This approach also bears some resemblance to the previous one. The idea here is to confound glioblastoma by alternating several drugs already on the market.

Phase 1/2a study on Lisavanbulin Published in Journal Cell Reports Medicine
Results have been published from the Phase 1/2a study of Lisavanbulin, an oral molecule that crosses the blood-brain barrier and transforms into Avanbulin, an agent that targets tumor cell microtubules. The study defined the optimal dose at 30 mg/day and demonstrated a favorable safety profile. Clinical results are mixed: some patients experienced complete or partial remission, and two maintained their response for over four years, while in most cases the disease progressed. The authors emphasize the need for larger studies and the identification of biomarkers to select the most responsive patients. This study presents several interesting aspects. The first is the technique for crossing the blood-brain barrier. The second is the realization that, given that glioblastoma is multifaceted and therefore varies from patient to patient, it is necessary to select the glioblastoma’s genetic profile to make the results of these studies more effective. Otherwise, we will continue for years with the STUPP protocol alone, which we know only prolongs survival but does not cure glioblastoma. The alternative is just the cocktail approach as in the case of the study reported above.

Value of artificial intelligence in neuro-oncology
An article published in The Lancet Digital Health explores the growing role of artificial intelligence in neuro-oncology, with a particular focus on glioblastoma. Neural networks and deep learning algorithms are used to accurately segment tumors, calculate their volume, and compare pre- and post-treatment images, providing more precise and faster measurements than traditional methods. The authors emphasize the potential of AI to support clinical decisions and improve the assessment of treatment response, but also highlight the need for large-scale validation and integration into clinical workflows to ensure its reliability and widespread adoption.

Novocure Announces Coverage of Tumor Treating Fields (TTFields) Therapy for Patients with Newly Diagnosed Glioblastoma in Spain
In Spain, the Ministry of Health has decided that adult patients with newly diagnosed glioblastoma who meet the eligibility requirements will be able to access Tumor Treating Fields (TTFields) therapy through the National Health Service. TTFields, or the Optune device, is a therapy based on low-intensity electric fields that interrupt the division of tumor cells. The treatment is administered via wearable devices. Among the European countries that already reimburse TTFields are Austria, France, Germany, Sweden, and Switzerland; with this decision, Spain joins the list. In Italy, as you know, unfortunately, the situation is fragmented, and the device is authorized or denied depending on the local health authority, which creates an absurd and unjustified inequality. We all know that the device is expensive and won’t save our lives, but it certainly does extend survival by several months, and this is very, very important for patients.

Thanks to everyone who has helped and continues to help us keep the volunteer organization alive and develop our projects, always focused on supporting patients and their caregivers. As you may have read, specialist training has begun for the “Hope and Courage” project. That’s all for this issue of research news. Best of luck to all those battling glioblastoma and their loved ones!