Pinworm drug, Mebendazole, targets cancers like GBM and osteosarcoma

Pinworm drug, Mebendazole, targets cancers like GBM and osteosarcoma
Mebendazole, oe Vermox, 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 (MBZ)
 
A 2019 meta-analysis (1) 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'. There was a previous review on 'Repurposed drugs' in 2014 which included Mebendazole (2).
 
Unfortunately, in both, this is the sort of research always dissed by skeptics, Cancer Research and oncologists when it is for curcumin, vitamin C or berberine! It is simply not very strong research.
 
Let me simply quote parts of the 2018 meta-analysis - "Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters".
 
It seems to work with Chemo- and Radiotherapy - "Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response".  
 
There is a little in vivo research - "in vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival" Yes, there is a study where it seems to help Oxaliplatin in head and neck cancer (3).
 
Mebendazole also appears to starve worms and cancer cells of glucose. And 'it impedes cancer stem cells'.
 
The researchers clearly warned that more research was needed especially to discover which chemotherapy drugs MBZ might enhance or hinder.
 
There maybe another reason it is an anti-cancer agent. Fasciolopsis buski is an intestinal fluke in humans. It is quite common especially in South East Asia. How many people with cancer took a holiday in Vietnam, Thailand, Cambodia, India or China? Mebendazole kills these Helminthics (5). That's its day job.
 
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 was originally created for animals,  Mebendazole is effective and now 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% (4). 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. 
 
The Care Oncology Protocol
 
Mebendazole is one of the off-label drugs being used by Care Oncology in London, alongside metformin, atorvastatin, doxycycline and, sometimes, flarin. Their research has convinced them that it has anti-cancer action and it seems to cut blood sugar so it can be prescribed as one of their four regular drugs in an aim to stop a cancer feeding and spreading. To quote their American site, They are 'Targeting cancer's metabolic pathways'  By starving cancer cells of energy, they are making orthodox treatments more effective. They make little or no claim that Mebendazole attacks and kills cancer cells.

Mebendazole or Fenbendazole?

Since the de-worming of the rats with Fenbendazole led to the complete failure of the researchers to give them brain cancer, you might be forgiven for wondering why oncologists aren't using Fenbendazole rather than Mebendazole, when it seems more potent.

Fenbendazole is another anti-helminthic drug. It too kills worms. It has been used in research studies with far more cancers and there is reasonable research on about nine different cancers. 

Joe Tippens used Fenbendazole with CBD oil to beat his Grade 4 Stage 4 NSCLC. It's a famous story. But there's a problem. Fenbedazole is only licensed for use with animals. No one has ever bothered to ask for a License for human use. Doctors would be struck off if they prescribed Fenbendazole! It's that simple.

Go to: Fenbendazole and cancer 

Mebendazole Health 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. 

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. 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, and possibly sugar levels.
 
 
 
* * * * * * * 
 
References
 
1. Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature; Andrea Emanuele Guerini, Luca Triggiani et al.  Cancers (Basel)  2019 Sep; 11(9): 1284.  
2. Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent; Pan Pantziarka, Gauthier Bouche et al; ECANCERMEDICALSCIENCE 2014; 8: 443
3. Anthelmintic mebendazole enhances cisplatin's effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC); Fugui Zhang et al.  Oncotarget  2017 Feb 21;8(8):12968-12982
4. Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme; Neuro Oncol v.13(9); 2011 Sep 
5. The treatment of Fasciolopsis buski infection in children: a comparison of thiabendazole, mebendazole, levamisole, pyrantel pamoate, hexylresorcinol and tetrachloroethylene; Trans R Soc,Trop Med Hyg. 1985;79(4):513-5

 

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