What is it about?
Most breast cancers (about 70%) depend on the hormone estrogen to grow, but scientists have lacked animal models that faithfully reproduce this disease. In this study, we developed a new CRISPR-based method to edit cancer genes directly in the mammary glands of rats. The resulting tumors closely resemble human estrogen receptor-positive (ER+) breast cancer in their appearance, hormone dependence, gene activity, immune environment, and response to endocrine therapy. Surprisingly, the same genetic changes produced very different tumors in mice, highlighting important biological differences between the two species.
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Why is it important?
Better disease models lead to better treatments. Although mice have been the mainstay of cancer research for decades, they rarely develop tumors that resemble the most common form of human breast cancer. Our rat platform fills this long-standing gap by providing genetically defined models that closely mimic human ER+ breast cancer. These models will help researchers better understand how this disease develops, why some tumors become resistant to hormone therapy, how the immune system influences cancer progression, and how new therapies can be tested before they reach patients.
Perspectives
For many years, researchers have accepted that mice are the default animal model for cancer research. Our findings show that this assumption does not always hold true. By combining modern genome editing with the biological advantages of rats, we demonstrate that rats can model important human cancers that mice cannot faithfully reproduce. We hope this work encourages broader use of rat models in cancer research and accelerates the development of more effective treatments for patients with hormone-responsive breast cancer and other cancers that have been difficult to model.
Yi Li
Baylor College of Medicine
Read the Original
This page is a summary of: Rat somatic genome editing enables ER+ breast cancer modeling, Proceedings of the National Academy of Sciences, June 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2529653123.
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