TcdBFBD, derived from a toxin found in Clostridium difficile, was tested in mouse models that mimicked different subtypes of breast cancer.
A series of experiments with the narrow-spectrum Wnt signaling inhibitor TcdBFBD were conducted in several mouse models mimicking different types of breast cancer, such as basal-like and luminal-like, that are found in humans. TcdBFBD is derived from a toxin found naturally in Clostridium difficile (C. diff).1
Although certain subtypes of breast cancer can be targeted with special medications, others can only be treated with standard chemotherapy. However, in some patients, chemotherapy may lead to the growth of stem cell-like cancer cells that are resistant to drugs. Prior research indicated that medications that inhibit a specific biological process called Wnt signaling could potentially combat these cells, but the potential benefits have been overshadowed by damaging adverse effects (AEs), particularly on bone density.1
The AEs are a result of the 10 different versions of the Wnt signaling receptor that have distinct functions. Researchers have recently developed new Wnt signaling inhibitors that can reduce the number of AEs by targeting only 3 of the 10 receptors; however, it is unclear how effective these narrow-spectrum Wnt signaling inhibitors will be at treating cancer.1
Aina He of Shanghai Jiaotong University Affiliated Sixth People’s Hospital in China, who conducted the series of experiments, found evidence that TcdBFBD helped suppress tumor growth and reduce activity of stem cell-like cancer cells in the mice without bone density-related AEs. In addition, TcdBFBD demonstrated that it can synergize with the standard chemotherapy drug cisplatin to inhibit both basal-like and luminal-like breast cancer tumors in mice.1
The findings provide introductory evidence for the potential therapeutic promise of narrow-spectrum Wnt signaling inhibitors such as TcdBFBD. The authors note that additional research is needed to further investigate their efficacy in humans, examine how TcdBFBD may synergize with cancer treatments that are not cisplatin, and explore the effects in additional types of cancer such as ovarian cancer and oral squamous cell carcinoma. In addition, the study authors note that a limitation of TcdBFBD is that the bacterial protein induces neutralizing antibodies within the body, and prior exposure to C. diff infection could result in existing immunity and lower efficacy of TcdBFBD.1,2
1. Public Library of Science. Side-effect avoiding treatment shows early promise against breast cancer in mice. News release. November 9, 2023. Accessed on November 20, 2023. https://www.sciencedaily.com/releases/2023/11/231109141428.htm
2. He A, Tian S, Kopper O, et al. Targeted inhibition of Wnt signaling with a Clostridioides difficile toxin B fragment suppresses breast cancer tumor growth. PLOS Biology. 2023;21(11):e3002353-e3002353. doi:10.1371/journal.pbio.3002353