Novel therapy reduces tumor growth in models of triple-negative breast cancer

Researchers at the University of California San Diego School of Medicine have identified a promising new therapy for triple-negative breast cancer (TNBC), which is among the most aggressive and difficult-to-treat forms of the disease. Their approach employs an antibody-drug conjugate - a delivery system that uses an antibody to identify cancer cells and deliver a highly potent chemotherapy directly into those cells without harming surrounding healthy tissue. Antibody-drug conjugates make it possible to use chemotherapy drugs that are too toxic to deliver on their own, offering a promising avenue for treating the most difficult cancers.

In 2025, an estimated 316,950 women and 2,800 men will be diagnosed with invasive breast cancer. TNBC accounts for about 10-15% of all breast cancer cases, and it is widely considered the most difficult breast cancer subtype to treat. This is because TNBC tends to grow and spread more quickly than other forms of breast cancer, and it typically fails to respond to therapies that work in other subtypes, such as hormonal therapies. As a result, survival rates for TNBC tend to be lower than for other breast cancers. Additionally, TNBC disproportionately affects younger women, Black women and those with certain genetic mutations.

Key findings from the new study include:

• A cell-surface protein called FZD7 is present on cells with high tumor-initiating potential in TNBC.
• By engineering an antibody-drug conjugate to target cells with FZD7, the researchers significantly reduced tumor growth in mouse models without observable toxicity.
• In mouse-derived organoids - 3D models of organ tissue - cells with FZD7 were more aggressive and more sensitive to the treatment than other tumor cells.
• The approach was also effective in human TNBC cell lines. 

While it will take further research to advance the treatment into the clinic, the study results suggest that targeting tumor-initiating cells through FZD7 could offer a new path forward for patients with aggressive breast cancers that do not respond to existing therapies. The research team believes this strategy may pave the way for more precise, effective treatments for TNBC, and the approach could also one day be leveraged against other cancers with similar biology. 

The study, published in Proceedings of the National Academy of Sciences, was led by Dennis A. Carson, M.D., professor of medicine and Karl Willert, Ph.D., professor of cellular and molecular medicine, both at UC San Diego School of Medicine. The research was supported by grants from the National Institutes of Health, The Mary Kay Foundation, and Curebound. The researchers declare no competing interests.