Botulinum Neurotoxin-A Inhibits Tumor Growth in a Triple-Negative Breast Cancer Preclinical Model

Triple-negative breast cancer (TNBC) continues to be a medical challenge requiring multiple treatment options. SV2A, a protein involved in vesicular release, has emerged as a promising biomarker for various cancers. Research shows that botulinum neurotoxin type A (BoNT/A), which binds to SV2A, the BoNT/A receptor, can inhibit the growth of prostate and breast cancer cells, suggesting its potential as an alternative treatment for breast cancer. The purpose of this study was to determine the potential of BoNT/A to inhibit tumor growth in a mouse preclinical model. BoNT/A was evaluated for its effects in an in vitro model employing 4T1 cells and in an in vivo model of orthotopically inoculated 4T1 cells in BALB/c mice. BoNT/A inhibited the proliferation of 4T1 cells, which express the SV2A protein; decreased tumor growth in the preclinical model; and decreased inflammation, associated with fewer blood neutrophils and monocytes, suggesting an immunomodulatory and anti-inflammatory effect. The effect of BoNT/A on the TNBC model supports its use as a repurposed drug for this type of aggressive cancer. Our results emphasize the significance of the SV2A receptor and its interaction with BoNT/A as promising therapeutic targets, particularly for TNBC.