For $12,000, a company grafts a patient’s cancer into rodents and tests drugs on them. At a laboratory in Baltimore, hairless mice kept in racks of plastic crates are labelled with yellow cards, each identifying a person fighting cancer. These mice are cancer “avatars”—the lumpy tumors visible under their skin come from actual patients.
The technology is a twist on personalized medicine that’s being developed by Champions Oncology. The company, based in New Jersey and Maryland, has started offering mouse avatars directly to patients, at a cost of $10,000 to $12,000. Insurance companies don’t yet pay for the technology, which remains experimental.
In the service Champions is selling, doctors first remove a piece of a patient’s tumor during a surgery or biopsy. Then they ship it to the company, where it gets grafted under the skin of an immune-deficient mouse. Because the rodents have impaired defenses, the human tumor is able to grow. Parts of it can be removed and implanted in additional mice.
The data from the avatars is potentially life-saving, since the choice of what drug to give a cancer patient is often made by guesswork or trial and error. “Generally, the drugs we give to patients are more likely to not work than to work,” says Justin Stebbing, an oncologist at the Imperial College London, who has been involved in medical studies of Champions’s technology. The results from the personalized mice, he says, “give patients an additional layer of confidence.”
Cancer avatars are part of a wider effort to carry out experiments on people’s tumors outside their bodies. Some researchers have created fruit flies that share the same gene mutations patients have. Another technology, still in development, looks to capture floating tumor cells from a person’s bloodstream, then grow and test them in culture dishes (see “A Laboratory for Rare Cells Sheds Light on Cancer”). Still further out, scientists have plans to grow mini-organs, complete with an immune system that matches the patient’s (see “Building an Organ on a Chip”).
Over the last few decades, study of cancer in mouse models has gained popularity. Sophisticated genetic manipulation technologies and commercialization of these murine systems have made it possible to generate mice to study human disease. Given the large socio-economic burden of cancer, both on academic research and the health care industry, there is a need for in vivo animal cancer models that can provide a rationale that is translatable to the clinic. Such a bench-to-bedside transition will facilitate a long term robust strategy that is economically feasible and clinically effective to manage cancer. The major hurdles in considering mouse models as a translational platform are the lack of tumor heterogeneity and genetic diversity, which are a hallmark of human cancers. The present review, while critical of these pitfalls, discusses two newly emerging concepts of personalized mouse models called “Mouse Avatars” and Co-clinical Trials. Development of “Mouse Avatars” entails implantation of patient tumor samples in mice for subsequent use in drug efficacy studies. These avatars allow for each patient to have their own tumor growing in an in vivo system, thereby allowing the identification of a personalized therapeutic regimen, eliminating the cost and toxicity associated with non-targeted chemotherapeutic measures. In Co-clinical Trials, genetically engineered mouse models (GEMMs) are used to guide therapy in an ongoing human patient trial. Murine and patient trials are conducted concurrently, and information obtained from the murine system is applied towards future clinical management of the patient’s tumor. The concurrent trials allow for a real-time integration of the murine and human tumor data. In combination with several molecular profiling techniques, the “Mouse Avatar” and Co-clinical Trial concepts have the potential to revolutionize the drug development and health care process.