Northwell Health - Feinstein Institute for Medical Research

For years, low-grade glioma — a tumor that originates from cells that support and protect the brain's nervous system — has been treated through a combination of surgery, radiotherapy and chemotherapy. The chemotherapy aspect of treating brain tumors has always been challenging due to one major obstacle. "The critical problem we face is that most anti-cancer drugs have trouble penetrating the blood-brain barrier," said Marc Symons, PhD, professor in the Karches Center for Oncology Research. "This natural defense mechanism protects the brain from substances in the bloodstream, but it can also keep medications and chemotherapy drugs from reaching their intended targets, namely tumors within the brain." Conventional treatment Vincristine, a drug commonly used in combination with other chemotherapy medications to treat brain tumors, is rather toxic and poorly crosses the blood-brain barrier. "When we used vincristine in animal models, we were shocked to discover that it simply didn't work," Dr. Symons said. "Although it is in use for many types of brain tumors, this study showed it to be ineffective." Dr. Symons explained the inaccurate assumption about vincristine's effectiveness may be due to its having been used in combination with other treatments — rather than being tested in isolation. Fortunately, Dr. Symons and his colleagues examined another drug that fared much better at treating brain tumors: mebendazole. An exciting new option Mebendazole is a medication typically used to treat parasitic pinworms. Dr. Symons' research found that mebendazole works similarly to vincristine in the way it kills cancer cells. However, in contrast to vincristine, it A new way to combat brain tumors Scientists at the Feinstein Institute are investigating an alternative use for a popular antiparasitic drug — as a brain tumor treatment. The benefits of repurposing One of the most expensive aspects of creating a new drug is the development stage. Creating a new medication from scratch is a complex process involving both preclinical and clinical studies that can take years. That's why drug repurposing has become so popular. Medications that have already been tested for safety and efficacy for one purpose can be brought to patients sooner. "There's a premium on trying to find drugs that were created to treat other diseases but can be repurposed to fight cancer," Dr. Symons said. "This skips the expensive drug development stage and can readily be tested in patients." While mebendazole may soon become the poster child of repurposing success, researchers all over the nation are excited about what other possibilities are out there. effectively crosses the blood-brain barrier and slows down brain tumor growth. "Our results showed that blood-brain barrier permeability really matters for the therapeutic effects of brain tumor drugs," Dr. Symons said. "In addition, the side effects associated with mebendazole appear to be milder than those associated with vincristine." Humans have used mebendazole with minimal problems for decades as an antiparasitic. In addition, the medication is extremely affordable compared with the cost of other cancer-fighting medications. "These findings are exciting, and it is obvious that mebendazole is a very good candidate to replace vincristine for the treatment of whatever brain tumor it's currently being used for," Dr. Symons said. "When comparing the two drugs, it's clear which option will benefit cancer patients the most." Visit FeinsteinInstitute.org/programs-researchers/cancer to learn about our work identifying causes of and discovering treatments for brain tumors. 6 / Volume 1, 2018 Innovation

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