A new antibody-drug conjugate targeting FZD7 shows promise for treating triple-negative breast cancer by delivering chemotherapy directly to cancer cells while minimizing damage to healthy tissue.

The study, published in PNAS, was led by Dennis A. Carson, M.D., and Karl Willert, Ph.D., at UC San Diego School of Medicine, with funding from NIH, The Mary Kay Foundation, and Curebound.

The PNAS paper highlights a collaborative translational research effort supported by NIH, The Mary Kay Foundation, and Curebound, and reports no competing interests.

The study is cited as Wu CCN, De Luna N, Hairston E, et al. FZD7 expression marks mammary tumor-initiating cells. PNAS. 2025;122(46):e2522465122.

Broader implications include applying the ADC targeting concept to other cancers with similar pathways and tumor-initiating cell populations, expanding impact beyond TNBC.

The research underscores tumor-initiating cell biology in TNBC and the potential for precision medicine to improve outcomes by limiting toxicities and improving durability of response.

Future work includes safety and efficacy testing in clinical trials, molecular profiling of FZD7 across patient populations, and exploring resistance mechanisms to ADC therapy.

TNBC accounts for about 10-15% of all breast cancers, is aggressive and often lacks effective targeted therapies, underscoring the need for new approaches.

TNBC tends to grow and spread quickly, with poorer survival rates, disproportionately affecting younger women, Black women, and those with certain genetic mutations.

In human TNBC cell lines and mouse-derived organoids, FZD7-expressing cells showed higher sensitivity to the ADC, supporting potential effectiveness across TNBC contexts.

In preclinical studies, the ADC inhibited tumor growth in mouse models with no systemic toxicity and demonstrated efficacy in 3D mouse mammary organoid cultures that mimic tissue organization and microenvironment.

Authors note that while clinical advancement requires more research, targeting tumor-initiating cells via FZD7 could offer a more precise therapeutic path for TNBC and may be adaptable to other cancers with similar biology.