Related Experiment Video
Updated: Jun 26, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Repurposing mebendazole against triple-negative breast cancer leptomeningeal disease
Adrian Rodrigues1, Sophia B Chernikova2, Yuelong Wang3
1Massachusetts General Hospital.
Purpose:
Triple-negative breast cancer (TNBC) is an aggressive subtype that often metastasizes to the brain. Leptomeningeal disease (LMD), a devastating brain metastasis common in TNBC, has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD.
Methods:
A small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, LMD was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging. MBZ was given orally at 50 and 100 mg/kg doses. MBZ bioavailability was assayed by mass spectrometry.
Results:
Bioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced tumor growth and extended survival in the LMD model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model.
Conclusions:
We demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC LMD. Our findings are concordant with previous efforts involving MBZ and central nervous system pathology and further support the drug's potential utility as an alternative therapeutic for TNBC LMD.
Insights
Mebendazole (MBZ) effectively reduced triple-negative breast cancer (TNBC) leptomeningeal disease (LMD) in mice. This study supports MBZ as a potential oral therapy for TNBC brain metastases.
Area of Science:
- Oncology
- Pharmacology
- Neuro-oncology
Background:
- Triple-negative breast cancer (TNBC) is aggressive and prone to brain metastasis, leading to leptomeningeal disease (LMD).
- LMD in TNBC patients has limited therapeutic options.
- The anti-helminthic drug mebendazole (MBZ) was investigated for its potential efficacy against TNBC LMD.
Approach:
- Screening of TNBC cell lines identified benzimidazoles as potential agents.
- In vitro migration assays assessed cell migration and MBZ effects.
- In vivo studies utilized a murine model of TNBC LMD induced by intracarotid injection of brain-tropic cells.
- Tumor growth and survival were monitored, with MBZ administered orally.
Key Points:
- TNBC exhibits higher migratory capacity than other breast cancer subtypes.
- MBZ significantly inhibited the migration of TNBC cell lines.
- MBZ treatment reduced tumor growth and extended survival in a murine model of TNBC LMD.
- MBZ showed no effect in a non-migratory breast cancer model.
Conclusions:
- Mebendazole (MBZ) demonstrated safety and efficacy in an animal model of TNBC leptomeningeal disease.
- These findings align with prior research on MBZ and CNS pathology.
- MBZ shows promise as an alternative therapeutic agent for TNBC LMD.
