Scientists in Houston, Texas have developed a new way to study the most common type of breast cancer — and the key to their discovery was switching from mice to rats.
Researchers at Baylor College of Medicine used a powerful gene-editing tool called CRISPR to create rat models that more closely resemble human estrogen receptor-positive breast cancer. This type of breast cancer, called ER+ for short, makes up about 70 percent of all breast cancer cases. Until now, scientists have mostly relied on mice for cancer research, but mouse models struggle to capture an important part of how human ER+ tumors actually behave.
The problem? Most mouse models of ER+ breast cancer use human tumors transplanted into the animal. Those transplanted tumors lack something crucial: the mouse's own immune system. Since the immune system plays a big role in how tumors grow and respond to treatment, studying tumors without it is like trying to understand a football game by only watching the quarterback.
"Our findings show rat models are a powerful way to study cancers that are not well studied in mouse models, which opens new opportunities to study tumor biology, therapeutic response and immune interactions in clinically relevant models," said Dr. Wen Bu, assistant professor at Baylor's Lester and Sue Smith Breast Center.
The Baylor team modified the CRISPR-Cas9 system, a tool that works like genetic scissors, to precisely edit cancer-causing genes in rats. The results were striking. While the same genetic changes created ER+ breast tumors in rats, they failed to do so in mice. The rat models closely mimicked human disease biology, how the cancer responds to therapy, and even the immune environment surrounding the tumor.
Dr. Yi Li, another senior researcher on the team, noted that the rat genome is actually closer in size and structure to the human genome than the mouse genome is. "Many human cancers, including breast and colorectal cancer, are better modeled in rats," he said. "Our method is easily adaptable to other organs."
The research, published in the journal Proceedings of the National Academy of Sciences, represents just the beginning. Co-senior author Dr. Xiang Zhang, who directs the Lester and Sue Smith Breast Center, said the work will "lead to many other downstream studies that will impact the field of cancer research."
In other words, the humble rat — often overshadowed by its smaller cousin the mouse in laboratory settings — may now help scientists understand and treat one of the most common cancers affecting women worldwide.