Faced with the failure of current treatments for the most aggressive brain tumours, a team from Grenoble and Marseille in France has unveiled an innovative dual therapy combining two generic cancer drugs, mebendazole and bumetanide. The first kills cancer cells and the second blocks hyperactivity and metastasis. The combination has been patented by B&A-Oncomedical, a start-up dedicated to tumour treatments. Successfully tested in preclinical studies and validated in a clinical trial, this approach, the results of which are published in two scientific journals (Cancer Research and Annals of Case Reports), could open up a new avenue in the treatment of the most aggressive brain tumours, targeting both the tumour and its pro-invasive environment.
Grenoble/Marseille, 10 July 2025 – Despite advances in neurosurgery, radiotherapy and imaging, aggressive brain tumours, particularly glioblastomas, remain highly resistant to treatment and associated with a poor prognosis. A French team based in Grenoble and Marseille, led by Prof. François Berger (Grenoble University Hospital – INSERM U1205) and Prof. Yehezkel Ben-Ari (B&A-Oncomedical, Marseille), is pioneering a new therapeutic approach based on a combination of two generic anticancer drugs with complementary effects, acting on different targets: mebendazole and bumetanide.
A novel dual mechanism of action
There is currently no effective treatment for brain tumours, particularly glioblastomas (GBMs), with a low life expectancy after chemotherapy and radiotherapy. Innovations in immunotherapy and CAR-T cells are beginning to show promising results in peripheral cancers, but have not been shown to be effective in brain tumours and are very expensive, which is a problem for wealthy countries and makes them inaccessible to most countries.
Why does the brain stand out from the rest? It appears that reactive plasticity plays a major role. Brain tumours are invaded by neighbouring cells, which form synaptic connections, generating cellular hyperactivity that worsens the prognosis. In short, the tumour is not a closed world and the surrounding cortex is not inert. As always, neurons sprout and invade the neighbourhood, including by forming aberrant connections. Even more impressive, these neurons outside the tumour become ‘young’ again, endowed with the properties of immature cells. Thus, GABA, which inhibits adult neurons and excites young ones, regains its ‘youth’, exciting the tumour cells due to high levels of chlorine and excessive activity of our friend, which I have often mentioned: the NKCC1 cotransporter, which, when hyperactive, increases chlorine levels in the neuron. As a result, this aberrant connection generates neuronal hyperactivity and epileptic activity, which increase the severity of the tumour. In fact, a large body of data illustrates the importance of cellular activity in the metastatic process. Clearly, we cannot treat the tumour alone; we must also block the hyperactivity of the surrounding area.
Based on this dual requirement, I suggested to my colleague Dr Berger (Grenoble University Hospital) that we conduct trials based on a combination of two generic drugs: bumetanide, which blocks NKCC1 and thus attenuates/blocks hyperactivity, and mebendazole, an antihelminthic drug known for its anti-cancer properties, which works by destroying the cell skeleton. A bibliographic study confirms the very promising effects of bumetanide, particularly in treating glioblastomas, a particularly severe form of cancer that is completely resistant to drugs. To destroy tumour cells, a molecule commonly used to treat intestinal worms (taenia tecta) has emerged as an effective treatment, as it acts on the cell cytoskeleton. A team of researchers at the University of Baltimore (USA) has conducted pilot clinical trials showing a beneficial effect on glioblastoma. It seemed important to me to combine the two agents in order to increase their effectiveness through a dual action. This new idea has been validated by the granting of a worldwide patent on the use of this combination in the treatment of cancer.
Additional preclinical and clinical results
Preclinical studies have been conducted on animal models and then on post-operative human tissue (glioblastomas, meningiomas, metastases, etc.). They confirm the synergistic effect of the combination of the two molecules on cancer cells: together, they destroy the majority of tumour cells and block the surrounding hyperactivity, with greater efficacy than each molecule used alone. The results were published in the Cancer Research Journal and can be viewed here: www.sciencepg.com/article/10.11648/j.crj.20251303.12
A notable clinical case published in Annals of Case Reports, by Gavin Publishers, shows similar results in a patient with an inoperable metastatic brain tumour who had failed all other treatments and received this combination as a compassionate use treatment. The result: rapid disappearance of pain, improvement in motor and visual functions, and significant reduction in tumour size within two months, with no notable side effects. The clinical improvement was maintained for seven months. The article is freely available online here:www.gavinpublishers.com/assets/articles_pdf/Treating-Aggressive-Brain-Tumorswith-the-Combo-BumetanideMebendazole-A-New-Cytotoxic-Anti-Invasive-Network-Strategy.pdf
Real hope thanks to treatments already available
This simultaneous anti-invasive and cytotoxic approach marks a turning point: it targets not only tumour cells, but also the brain ‘network’ that promotes their progression. Above all, it stands out for its use of generic drugs that are already available on the market, making it potentially accessible and inexpensive and paving the way for precision medicine based on the repositioning of existing molecules. The combination has been patented by B&A-Oncomedical, a start-up dedicated to tumour treatments. A phase I multicentre trial (BM-CAN) is now being prepared to confirm the safety and efficacy of this dual therapy in combination with standard treatments.
Did you know? A compassionate use trial allows a treatment that has not yet been approved to be administered to a patient in critical condition when all conventional treatment options have failed. This exceptional measure, supervised by the health authorities, offers an additional chance to patients with no other recourse, while allowing valuable clinical data to be collected for research purposes. It is in this context that the combination of mebendazole and bumetanide has been tested in a patient with an inoperable brain tumour.
Real hope thanks to existing treatments
This dual anti-invasive and cytotoxic strategy marks a turning point: it targets not only tumour cells, but also the brain ‘network’ that promotes their progression. Above all, it is based on well-known, generic drugs that are therefore accessible and can be mobilised quickly.
