Avatar Mice: How These Rodents Are Advancing Cancer Therapies

When Holly Boehle heard that she would be paired with a mouse in her breast cancer study two years ago, she was intrigued.

"When I first heard about it, I thought: 'There's gonna be little Holly mice running around.'"

Those mice may also be the key to determining optimal treatments for Boehle if her cancer, which is now in remission, ever comes back. "Now they'll know what specifically works for me," she says. "It's pretty exciting to think about."

The trial Boehle enrolled in is called BEAUTY, which stands for "breast cancer genome guided therapy." Launched in 2013, it's based at the Mayo Clinic in Rochester, Minnesota. Using avatar mice -- mice with patients' tumor samples growing inside of them -- researchers are able to study various treatments and determine which might be best tailored to each patient.

"When we treat the mice with drugs, that is very much a mirror of what happens in patients," says Judy Boughey, a breast surgeon at the Mayo Clinic. Boughey is a co-director of the study, which enrolled 140 breast cancer patients.

Using mice avatars is one of the latest developments in personalized medicine: By literally pairing patients with mice, scientists can determine the treatments that work for individual patients, as well as identify genetic markers common to patients, information that could be used for drug development.

Boughey and the other study leader, Matthew Goetz, an oncologist at the Mayo Clinic, took samples of patients' tumors before the patients were treated, and then quickly injected their tumor tissue into the mice, allowing the tumors to grow for days to months. Once tumors had reached a certain growth point, researchers then cut them up and injected those samples into more mice. The idea is to have generations of mice in which patients' tumors are growing, so researchers can try out multiple treatments on the mice at the same time, and examine the results side by side.

That's something scientists could never study in a single patient, says Carol Bult, deputy director of the Jackson Laboratory Cancer Center in Bar Harbor, Maine. Bult is co-leading the Maine Triple-Negative Breast Cancer Study, which focuses on an aggressive form of breast cancer, triple negative, which disproportionately affects younger women and is often resistant to treatments and frequently recurs. The study, which uses mice avatars, tests four drugs, the first of which is standard treatment. The other three are experimental. In another pediatric cancer study, Bult is studying two drugs side by side, but flipping the order, another approach that is often tested in animals.

"The mice are basically serving as stand-ins [for patients], so the efficacy of particular treatments can be borne by mice instead of patients," Bult says.

Building Mouse Models, One Patient at a Time

The Maine Triple-Negative Breast Cancer Study also illustrates the power of using avatar mice to combat recurrence, since researches can launch an accelerated search for drugs uniquely suited to keep their patient's tumors in check.

In addition to helping physicians find optimal treatments to stop recurrence, another primary goal of using avatar mice is to accelerate the hunt for treatments that can stop the spread of cancer, or metastatic disease -- cancer that sweeps throughout the body and is usually considered incurable, Bult explains. The researchers are also collecting genomic information -- essentially the genetic fingerprint of a person's tumor -- to help inform the development of new treatments. "The information we get is not only useful for that one patient; but we also store all of the data into a knowledge base that allows us to draw correlations between tumors and response to treatments," Bult says.

This approach is especially promising for treatment-resistant cancers, such as small cell lung cancer and lung cancer with the EGFR mutation, Bult says, adding that a bladder cancer study is also underway. Bladder cancer can be very hard to treat if it recurs outside the bladder.

While the avatar mice might be promising for patients, particularly those with advanced or recurrent cancer, using them as patient proxies is not widespread in clinical medicine yet, says Len Lichtenfeld, Deputy Chief Medical Officer for the American Cancer Society.

"What we always have to be so careful about is that something that looks encouraging in the lab may not translate to something that works for patients in the clinic," Lichtenfeld says. Still, he concedes, the the information being gathered from this research "may help us predict response on a much wider scale in the future."

The approach can also be costly, with avatar mice costing patients an average of $10,000 to bank the tumor tissue and try out three to five drugs, which insurance does not cover. Companies such as Champions will make a mouse avatar from a patient's tumor, do drug testing on that tumor and then give the treatment results back to the oncologist. The study of mice as human understudies is also expensive for institutions. At certain centers such as the Dana-Farber Cancer Institute in Boston and Columbia University in New York, there are mouse hospitals, where mice have their own nurses, mouse-size MRI machines and most importantly, the cutting-edge drugs they will be given so scientists can better understand human disease.

The Magic of Mice

Mice have been used in medical research for decades, but more recently, techniques for matching them to human disease have improved. Mice are particularly amenable subjects for studying recent cancer therapies, such as immune therapy, which boosts the immune system to attack cancer cells, because some mice naturally have weakened immune systems, and scientists can easily introduce other defects in them for study, says Megan Sykes, a professor of medicine, microbiology, and immunology and surgical sciences at Columbia University in New York City. Scientists can also then generate human-like immune systems in the mice, and test immune therapy on them.

Sykes and her colleagues are also using mice as human proxies to study autoimmune diseases like Type I diabetes. By manipulating mouse immune systems, the researchers are able to observe the onset of Type 1 diabetes, in which the body attacks its insulin-making cells, and watch as the disease progresses to full-blown diabetes; they can then tinker with different ways of interrupting or reversing this process, which may someday be applicable to people.

This approach, she says, has "broader applications for any auto-immune disease."

And mouse models, Bult adds, certainly trump cell culture models for studying human disease. "[Cell culture models have] proven to be a rather poor surrogate to human cell response," she says. "I think the numbers are 90 percent of drugs that go into phase I clinical trials die there. If we can do anything to improve the success of these treatment options, even a few percentage points, we'll have a huge impact."

Kristine Crane is a Patient Advice reporter at U.S. News. You can follow her on Twitter, connect with her on LinkedIn or email her at kcrane@usnews.com.