Possible breakthrough in GBM therapy

Is this the breakthrough in treatment of glioblastoma that has been evading us now for decades?

Despite very good and well-justified efforts to challenge, for example, 3-D cultures of patient-derived tumor stem cells with the battalion of approved drugs used in cancer therapy nothing has worked.  The debate has raged.. Is it the failure to reach the tumor? Is it inflammation, despite the BBB leakiness that follows? Is it the dendritic and diffuse nature of the disease? Or, and so on?

Here then is something completely novel: a combinatorial approach based on two small molecule drugs: an anti-epileptic, bumetanide, and an anti-helminthic, mebendazole, that shows real promise in killing glioblastoma (GBM) cells.  The work led by Yehezkel Ben-Ari of Brain Tech, INSERM and start-up Ba-oncomedical (both of Grenoble, F) showed significant reduction in cell hyperactivity and increased cell death with the combination therapy against cell cultures and animal models than that achieved by single agent or DMSO control. 

Amongst the investigations performed, DRAQ7 was used in parallel with caspase-3 detection to monitor apoptotic cell death in 3-D co-cultures of neural cells and GBM tumor-derived cells - by flow cytometry, following tumoroid digestion.

The authors' assert that the combination of a NKCC1 inhibitor (e.g. bumetanide) and a microtubule disruptor (e.g. mebendazole) requires further clinical exploration.

At the very least this research suggests that we need to look much wider in our search for a GBM treatment that gives a useful increase in patient survival. That will entail bold investments in industrial scale biology, AI/ML interrogation and a deeper understanding of the GBM tumor milieu to identify lethal susceptibilities similar to that described in the current work.

Reference:
Bourgeois et al. Dual Targeting of Brain Tumors and Their Environment by Bumetanide and Mebendazole. Cancer Research Journal 2025, Vol. 13, No. 3, pp. 98-112.

DOI:10.11648/j.crj.20251303.12