News in the Research in the Second Two-Months of 2024

This is the twenty-fifth article of the project which aims to periodically (every two months) collect the latest research on possible treatments for glioblastoma multiforme. Below I list the news that we considered most significant to emerge in the last two months. As with the previous articles in the series, each piece of news will be preceded by the original title with a link to the source and followed by a short comment. The criterion with which the news is chosen is always to generally include only news relating to research in the clinical phase, unless the potential of the research for the treatment of glioblastoma is truly remarkable.

Berberine as a potential enhancer for 5-ALA-mediated fluorescence in glioblastoma: increasing detectability of infiltrating glioma stem cells to optimize 5-ALA-guided surgery
The prognosis of glioblastoma (GBM) is related to the residual volume of the tumor after surgery. In fluorescence-guided surgery, 5-aminolevulinic acid (ALA) is used to maximize resection while avoiding neurological morbidity. However, not all tumor cells, especially glioma stem cells (GSCs), show 5-ALA-mediated fluorescence (5-ALA fluorescence). The authors searched for repositioned drugs that affect mitochondrial functions and energy metabolism, identifying berberine (BBR) as a potential enhancer of 5-ALA fluorescence. In this study, they investigated whether BBR can enhance 5-ALA fluorescence in GSCs and whether BBR can be applied to clinical practice as an amplifier of 5-ALA fluorescence. The result is that BBR enhanced 5-ALA-mediated PpIX fluorescence. BBR is a clinically used drug without side effects. It can therefore be stated that BBR significantly improves fluorescence-guided surgery and the same consideration exists for photodynamic therapy.

Early clinical trial results show ‘dramatic and rapid’ regression of glioblastoma after next generation CAR-T therapy
This is one of those stories that ended up in all the newspapers. Our job is to clarify. Among other things, we organized a video conference on the topic of immunotherapy on May 21st at 6:00 pm. In an article published in the New England Journal of Medicine, researchers at Mass General Cancer Center shared results from the first three patient cases of a Phase 1 clinical trial evaluating a new approach to CAR-T therapy for glioblastoma (GBM ). The study, known as INCIPIENT, was designed to evaluate the safety of CARv3-TEAM-E cells in patients with recurrent GBM. Just days after a single treatment, patients showed notable reductions in their tumors, with one patient achieving nearly complete tumor regression. Over time, the researchers observed tumor progression in each of these patients, but because the strategy’s preliminary results are promising, the team will look for strategies to extend the duration of response. Bryan Choi, M.D., Ph.D., neurosurgeon and associate director of the Center for Brain Tumor Immunology and Immunotherapy, said that combining CAR-T therapy with other methods is a potentially more effective approach to treating glioblastoma. The team is considering serial infusions or preconditioning with chemotherapy to prolong the response.

The detrimental effect of biopsy preceding resection in surgically accessible glioblastoma: results from the national cancer database
This study investigated the impact of performing a biopsy before definitive resection in patients with surgically accessible glioblastoma (GBM). The study analyzed 17,334 patients with GBM from the National Cancer Database (NCDB) from 2010 to 2014. Patients were categorized into two groups: “direct resection” and “biopsy followed by resection.” Outcomes evaluated included overall survival (OS), 30-day readmission/mortality, 90-day mortality, and length of stay (LOS). What emerges from the study is that preoperative biopsies for surgically accessible GBM are associated with worse survival, even when followed by resection, compared to patients who underwent direct resection. The findings suggest that avoiding preoperative biopsies when possible may improve survival outcomes in these patients.

REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma
In the phase II REGOMA trial, regorafenib showed promising activity in patients with relapsed glioblastoma. This study prospective, multicenter and observational was conducted to confirm REGOMA data in a real-world setting. Between September 2020 and October 2022, 190 patients with relapsed glioblastoma were enrolled in 30 oncology centers in Italy. Median OS was 7.9 months and median PFS was 2.6 months. The radiological response was partial in 13 patients (7.3%) and stable disease in 26 patients (14.6%). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. This large observational study showed a similar OS compared to the REGOMA study, substantially confirming its results..

That’s all for this research news issue. Best of luck to all those who are fighting glioblastoma and their loved ones!