Scientists redesign common deworming drug to kill cancer cells

What is being hailed as a ‘cancer treatment breakthrough’ comes not from a brand-new experimental drug, but from a 40-year-old medicine used to treat worms. 

Researchers from Johns Hopkins University have patented a new form of mebendazole, called polymorph C, which may work much better against cancer than the versions currently available. 

Mebendazole is already a well-known drug that safely treats parasitic worm infections in humans and animals. 

The new crystal form, polymorph C, seems to get into tumors more effectively, including brain tumors, which are usually very hard to treat because most drugs cannot pass through the protective blood-brain barrier. 

According to the patent, an oral formulation with at least 90 percent polymorph C can reach cancer cells at higher concentrations than standard mebendazole, potentially making it more powerful. 

The inventors said this new form could be used to treat many different types of cancer, from brain tumors like gliomas and medulloblastomas to breast, colon, lung, pancreatic and thyroid cancers, and possibly even help prevent cancer in people at high risk. 

In experiments with mice, polymorph C reached effective levels inside tumors and showed stronger tumor-suppressing effects than other forms of mebendazole. 

The researchers also suggested combining it with another drug, elacridar, which can block cancer cells from pumping out the drug, making it work even better. 

The patent, awarded on September 7, 2021, states: ‘As an oral drug, mebendazole polymorph C is a superior form, and it reaches the brain and brain tumors in effective concentrations. Efficacy is further improved by combining mebendazole with a P-glycoprotein inhibitor.

‘Mebendazole may also be used for therapy of other cancers, as well as a chemopreventative agent.’ 

Another proposed approach is pairing mebendazole C with anti-inflammatory drugs such as celecoxib or sulindac. 

Chronic inflammation is linked to cancer, so this combination could help reduce the risk of tumors forming in particularly vulnerable people. 

Because mebendazole has been safely used for decades, this new formulation could move into clinical trials faster than most brand-new cancer drugs, according to the researchers.

The patent, filed by Gregory Riggins, Renyuan Bai, Verena Staedtke, Avadhut Joshi and Tara Williamson, focuses on a simple but important idea that mebendazole comes in three slightly different structures, called polymorphs, and one of them, polymorph C, behaves very differently in the body. 

It can travel to the brain more effectively and reach tumors at concentrations that may actually be effective at killing cancer cells. 

This is unusual because most chemotherapy drugs cannot cross into the brain at all.

When mice were given oral doses of polymorph C, the researchers found that polymorph C reached high enough levels in both the blood and the tumors to have anti-cancer effects. 

The team described the results as ‘increased tumor suppression’ with ‘acceptable toxicity,’ meaning the drug killed cancer cells without causing harmful side effects in the animals.

The patent also addressed a common problem in cancer treatment: drug resistance.

Some cancer cells have molecular ‘pumps’ that push drugs out before they can work. 

Using mebendazole C together with a P-glycoprotein inhibitor helps the drug stay inside the cancer cells longer, increasing its effectiveness.

In tests with mice that had aggressive brain tumors, the combination of polymorph C and elacridar extended survival compared to polymorph C alone. 

Even after a single oral dose, the drug stayed in the brain for several hours at levels higher than what is needed to kill cancer cells in lab tests. 

However, prolonged treatment with both mebendazole and elacridar caused some side effects, including significant weight loss and even death in some mice. 

This suggested that while the combination was very effective, careful attention to dosing and treatment length will be essential in future studies, the researchers noted. 

The range of cancers covered in the patent is broad, including brain tumors, colorectal cancer, breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, thyroid cancer, melanoma, and sarcomas. 

The challenge with traditional mebendazole has been inconsistent absorption in the body, but the new polymorph C formulation is designed to overcome that problem.

A recent preclinical study confirmed that mebendazole polymorph C not only reaches high levels in the brain but also concentrates effectively within brain tumors, significantly improving survival in mice with gliomas and medulloblastomas. 

The researchers also tested combining polymorph C with elacridar, a drug that helps chemotherapy stay inside tumor cells, and found that this pairing further extended survival, although higher doses caused some toxicity. 

These findings provided concrete, laboratory-based evidence supporting the patent’s claims that polymorph C can penetrate tumors more efficiently than other forms, highlighting its promise as a potent brain cancer therapy. 

One reason this discovery is exciting is mebendazole’s long history of safety.

 Approved in the early 1970s, it is well-understood by doctors and even available over the counter in some countries. 

This means researchers can focus on testing effectiveness against cancer, rather than starting with unknown safety risks.

However, the team noted that just because the drug worked in mice does not mean it will automatically work in humans. 

Doctors will need to figure out the right dose, how the human body processes it and whether it interacts safely with other medications. 

The patent describes specific formulations, including granulated, coated, or micronized versions, to help the drug be absorbed better, all of which require further development.

If clinical trials can confirm the promise of polymorph C, mebendazole could become a rare example of a cancer therapy that is effective, affordable, and based on a drug doctors already trust. 

For patients facing some of the deadliest cancers, this old medicine may offer a surprising new way forward.