Pinworm drug, Mebendazole, targets cancers like GBM and osteosarcoma

Pinworm drug, Mebendazole, targets cancers like GBM and osteosarcoma
Mebendazole, a widely used anti-helminthic drug for treating pinworm infestations in humans, blocks tubulin, which normally causes more parasites to form because it is important in cell division; tubulin is also present in cancer cells and limited studies have shown effects with Glioblastoma (GBM), lung cancer and osteosarcoma.
 
Anti-cancer effects of Mebendazole
 
A 2019 meta-analysis of Mebendazole as an anti-cancer agent concluded that, in vitro, it inhibits direct cytoxic activity and may work with both radiotherapy and chemotherapy to produce an anti-tumour immune response. Unfortunately, this is the sort of research always dissed by skeptics, Cancer Research and oncologists when it is for curcumin, vitamin C or berberine! However, there is a little in vivo research, where MBZ, when used on its own or with chemotherapy, led to an arrest of tumour growth, reduction of metastases and increased survival.
 
Mebendazole also appears to starve worms and cancer cells of glucose.
 
The researchers however warned that more research was needed especially to discover which chemotherapy drugs it might enhance or hinder.
 
An accidental discovery of the anti-cancer effects of Mebendazol
 
Researcher Gregory Riggins at Johns Hopkins Cancer Center in Baltimore accidentally discovered that a similar drug, licensed for killing worms and parasites in animals (Fenbendazole) stopped his brain tumour experiments with mice - de-worming them with Fenbendazole stopped them being given brain tumours. In his experiments, all of the mice had been given brain tumour cells but the mice that had been de-wormed first with Fenbendazole didn’t develop any brain tumours! That was the animal-approved version of the drug, so he started looking at the human-approved version - Mebendazole.
 
How does Mebendazole work against cancer?
 
Mebendazole, or MBZ, also called Vermox, works against many types of parasitic worms (helminths) and their infections because it targets the synthesis of microtubules, by inhibiting tubulin polymerisation in their intestinal cells and killing them. It also starves the worms of glucose. It is taken by mouth and although itself originally created for animals,  Mebendazole is effective and has a long history of safety in humans.
 
Pinworms are an increasing threat to Americans with over 40 million developing an infection every year. Worm infections treated by Mebendazole include ascariasis, pinworms, hookworm, guinea worm and giardia.
 
So we know for certain that Mebendazole attacks microtubule formation in parasites. But microtubules are crucial to cancer cell formation also.
 
Microtubules are tiny fibres of tubulin protein that are involved in cell movement, cell division and mitosis (the transfer of the genome). Because each new created cell needs to be a copy of the parent, anything that disrupts the perfect copying can stop the whole process. University of California scientists have shown that the disruption of this process is how Taxol (paclitaxel) works, for example, although Taxol also attacks Bcl-2. 
 
Starving the cancer of glucose would also be a positive for Mebendazole.
 
Using drugs like Mebendazole off-label for cancer
 
There are many drugs like Mebendazole, which have been around for ages and so their safety profile is well understood. These drugs were created for use with other illnesses and conditions and many are now off patent and so are cheap. When they are used (repurposed) for cancer treatment they are being used 'off-label', that is, not for the original purpose defined on the label.
 
Many scientists argue, "Why look for expensive new drugs, when there are already cheap drugs available which can do the same job?" Big Pharma doesn't like this idea, of course, and so have no interest in this area. The usual skeptics come out to call off-label drug users 'quacks'. But if these drugs can do a job, (especially if their side-effects are minimal), why not give them a try? 

Mebendazole and GBM

So could Mebendazole be used to treat GBM, glioblastoma, the most deadly form of brain cancer, in humans?

Riggins then completed phase I clinical trials which primarily measure safety. And Mebendazole passed in humans – both children and adults. In 2011 Riggins was part of a larger pre-clinical trial that showed MBZ could increase survival times in glioma cell lines by as much as 67% (2). Again the latter finding is in vitro.

Mebendazole and other cancers

All this is not actually new news. Back in 1998, Professor Ben Williams used Mebendazole alongside other 'off-label' drugs metformin, melatonin, accutane and tamoxifen to beat his own Glioblastoma. 

Back in 2002, Mebendazole showed an effect against Lung cancer cells, causing dose-dependent apoptosis (cancer cell death). As a second part of this research, mice were given non-small cell lung cancer, and Mebendazole stopped the growth of the disease in vivo, with 80 per cent less metastases.

Work followed with adrenocortical cancer in vitro and in vivo in 2007 and the following year with melanoma, showing a similar pattern of results, as a thorough overview has shown(1).

By 2011, similar results were shown with osteosarcoma.
 
Two clinical trials are currently underway with brain tumours, one with high grade GBM (at Johns Hopkins) alongside Temozolomide; the other at Cohen's Children's Centre in New York, with low grade GBM.
 
If it works like Taxol, is there any research with breast cancer? The 2002 Lung Cancer study had a short piece on the effectiveness with breast cancer cells. In a 2010 study in HER2 breast cancer cell lines, mebendazole was shown to have an effect, albeit limited.
 
It's all a bit scant really, and much of it is in vtiro, but of course, funding is a major issue for proper clinical trials as the only people with the necessary funding are Big Pharma. Why would they support off-patent drugs?
 
Mebendazole, from research, does seem to inhibit BRAF, EGFR, ABL, ERK and MMP. 
 
Mebendazole is one of the off-label drugs being used by Care Oncology in London, alongside metformin, atorvastatin, doxycycline and, sometimes, flarin.

Go To: Repurposing old drugs to treat cancer

Warnings?

Not to be taken by pregnant women; and the antihistamine Cimetidine can significantly reduce its effectiveness. Abdominal pain can occur. The drug may also cause skin sensitivity and rashes.

Not a warning, but more of a problem: Mebendazole has poor bioavalability and only approximately 20% of the drug is absorbed into the blood stream, however, this can be improved by taking it with fatty foods. The lipophilic properties of the drug do, however, allow it to cross the blood brain barrier. 

Fenbendazole?

The original animal worm killer Fenbendazole, what happened to that? Well, one man, Joe Tippens used a protocol based around it and beat his stage 4, grade 4 NSCLC inside 3 months -

Go to: Fenbendazole and the Joe Tippens' Protocol 

Mebendazole - the bottom line
 
Yes, it seems to be good in research and in real life with brain tumours. For other cancers, the evidence is scant and often in vitro of the type  skeptics and oncologists shower with derision. There is better research on more cancers for Fenbendazole. But would an oncologist expect to keep his licence if he started prescribing a worm killer for cats and dogs to a 13 year old with a brain tumour? It is also very clear that we have no idea which chemo drugs it might enhance or hinder. But it does seem to damage microtubules, and reduce cancer cell oxygen.
 
* * * * * * * 
 
References
 
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158014/

 

 

 

 

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