Triple-Negative Breast Cancer CNS Metastases: Repurposing an Older Drug for New Use

By: Celeste L. Dixon
Posted: Friday, May 17, 2024

In the future, some patients with breast cancer may be treated effectively with mebendazole, a common antihelminthic drug in the benzimidazole class developed in the 1960s. Researchers have demonstrated in the murine setting that it is both safe and active as an oral agent in treating triple-negative breast cancer that has metastasized to the central nervous system (CNS). Melanie Hayden Gephart, MD, MAS, of Stanford School of Medicine, California, and colleagues reported on their preclinical research findings in the Journal of Neuro-Oncology.

Their findings support mebendazole’s potential use in slowing leptomeningeal disease. Triple-negative breast cancer frequently metastasizes to the CNS, and of all breast cancer subtypes, triple-negative breast cancer has the highest propensity to develop leptomeningeal disease.

The team claimed its study was the first to test mebendazole’s efficacy in aggressive CNS breast cancer metastasis, although previous investigators have examined the the drug’s effects on other CNS pathology. “Our data suggest that mebendazole targets cancers with high migratory capacity, and [it] may be particularly effective when these cancers spread into [the] leptomeningeal space,” wrote the investigators.

In the team’s brain metastasis mouse model studies, mebendazole reduced leptomeningeal spread and extended survival by effectively slowing down migration of triple-negative breast cancer cells and a companion brain-tropic derivative. Mebendazole, they said, “may function by selectively targeting migrating tumor cells,” noting the agent had no apparent effect in a model involving nonmigratory breast cancer cells.

Developed to treat gastrointestinal helminth infections, mebendazole is one of the world’s most commonly used medications. Of note, its bioavailability and efficacy are known to be influenced by fat intake—fat “strongly facilitates benzimidazole absorption,” wrote the authors. Those who study mebendazole for triple-negative breast cancer in the future must keep that fact in mind, because not doing so “could introduce substantial variability in drug efficacy across studies and potentially impact the outcome of clinical trials.”

Disclosure: The study authors reported no conflicts of interest.

Journal of Neuro-Oncology

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