Research News for the Second Two Months of 2021

This is the eighth article of the project which aims to periodically collect (every two months) the news of research on possible treatments for glioblastoma multiforme. Today I’m super happy … the site has exceeded 40,000 users (3 out of 4 from Italy) and this month it received more than 6,000 unique visitors for the first time!
Below are the news that I considered most significant. As for the previous articles in the series, each news will be preceded by the original title with a link to the source and followed by a short comment. The criterion by which the news is chosen is always to include in general only the news related to research in the clinical phase, unless the research potential for the treatment of glioblastoma is really important.
Help the fundraising campaign for CUSP-ND for Emanuele by sharing the link in order to spread the word and raise awareness as many people as possible. In this regard, have a look to the first news!

A Pilot Clinical Study of CUSP9v3: Nine Repurposed Drugs Combined With Temozolomide for the Treatment of Recurrent Glioblastoma
The study has so far involved 10 patients with recurrent glioblastoma. The aim of the study was to evaluate the toxicity of the 9 drugs. Ritonavir, temozolomide, captopril, and itraconazole were the drugs that most frequently required dose reduction or pause. The most common adverse events were nausea, headache, fatigue, diarrhea and ataxia. Progression-free survival after 12 months was 50%. The conclusions are therefore that the CUSP9v3 protocol can be safely administered to patients with recurrent glioblastoma multiforme under close monitoring. A randomized phase II study is being prepared to evaluate the efficacy of the CUSP9v3 regimen in glioblastoma which will also involve newly diagnosed patients (CUSP-ND).

Chemo for glioblastoma may work better in morning than evening
Chemo for glioblastoma may work better in the morning than in the evening. Although this is a small study, the difference in results is so large and there is no downside to switching from taking the drug in the morning to taking it before bed. Talk to your doctor and consider switching to morning intake!

Treatment approach and survival from glioblastoma: results from a population-based retrospective …
In a real-world setting, less than half of patients received full-cycle chemoradiotherapy, with a median survival comparable to clinical trial results. Survival was significantly worse in patients who received less intensive treatment. The results highlight a substantial risk of undertreatment of glioblastoma, especially in elderly patients.

Microglia, Stockholm syndrome and miraculous cures in glioblastoma patients
Although most patients survive less than two years after diagnosis, some patients survive for a long time. This study examined the gene expression profiles of glioblastoma specimens collected from approximately 900 glioblastoma patients from regions around the world to identify unique characteristics associated with so-called “exceptional responders” defined as glioblastoma patients who survive more than two years after the diagnosis. The result is that the single important difference is that these patients have a shortage of microglia and macrophages. Microglia and macrophages are specialized immune cells that act as scavengers to recognize and remove cells not normally found in a healthy brain, including cancer cells. It therefore appears that these cells are reprogrammed by the glioblastoma to transform from cells that fight cancer cells to cells that promote their growth. A sort of Stockholm syndrome. Fortunately, it seems that this sort of Stockholm syndrome of microglia and macrophages depends on the activation of a protein, PI3Kγ, which if deactivated restores the normal anticancer function of these cells. It seems that treatments targeting this protein are already being developed and can therefore transform all patients into “exceptional responders”.

Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply?
We think a phase 3 randomized controlled trial is the best way to understand if a drug works. We have seen several cases where a phase 1 or 2 study had spectacular results and then failed in phase 3. This article explains why patients who participate in clinical trials perform better than those who do not and this unfortunately has nothing to do with participating in the study. It is the entry criterion. The vast majority of glioblastoma patients are ineligible for clinical trials, and these people normally do worse than patients who are eligible. This also means that the results of a phase 3 study do not represent how the treatment would work in the general population of patients with glioblastoma. We must therefore rethink how we test drugs. We absolutely need to monitor all brain tumor patients as if they are participating in a trial to see how the treatments works on everyone, not just the select few. This is why I am increasingly convinced of the goodness of the project that I am about to launch, which I will call Glioblastoma Navigator. So stay tuned because very soon I will describe it in more detail!

That’s all for this two-month period. Best luck to all those fighting glioblastoma and their loved ones. I truly hope that despite the pandemic, this year will also be a year of significant progress in the fight against glioblastoma!