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n the end, the mice couldn’t save Rob Ford, the controversial former mayor of Toronto, who died of cancer this week at age 46.

Late last year, bits of Ford’s liposarcoma, a rare cancer of connective tissue he’d been battling since 2014, were transplanted into specially bred mice as part of a clinical trial at Toronto’s Mount Sinai Hospital. The idea was that tumors would grow in the bewhiskered “avatars,” and then the mice would receive different chemotherapies individually and in combinations. Seeing which treatments shrunk the tumors would help Ford’s physicians determine what drug to give him.

And all of this would happen while sparing the former mayor from having to endure chemotherapy after toxic chemotherapy until one worked.

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Cancer has become the chief proving ground for precision medicine. That generally means determining the genetic profile of a tumor, identifying mutations that might be driving it, and trying to disable those drivers with targeted therapies so as to slam the brakes on malignant cells’ uncontrolled proliferation.

Now “precision chemotherapy” aims to do that for old-line drugs.

Unlike the mutations that indicate which targeted therapy might succeed, there are no tumor characteristics that show which chemo has the best shot, said Dr. George Demetri, a sarcoma expert at the Dana-Farber Cancer Institute. That’s where the mice come in.

By early March, according to local news reports, Ford’s tumors had been growing in mice for about three months. His family said scientists would start testing chemotherapies on the avatars no later than mid-March. Ford did not survive long enough for that. (The hospital did not respond to requests for comment about Ford’s case.)

But hopes for cancer avatars — formally called patient-derived xenografts, or PDXs — are very much alive.

In January, oncologists at the Samsung Medical Center in South Korea announced the start of a large PDX trial for metastatic cancers. Last November, Toronto’s Mount Sinai began recruiting the first of a planned 30 to 40 cancer patients for the sarcoma trial that included Ford; results are expected in four years.

And in New York City, scientists are running a clinical trial that involves transplanting pieces of triple-negative breast cancers into mice and testing chemotherapies. That 140-person study, at the Icahn School of Medicine at Mount Sinai, began in 2014 and is scheduled to be completed in June 2017.

Both the Toronto and New York studies use a xenograft system developed by Champions Oncology, a Baltimore-based company founded in 2007. Its approach aims to avoid a pitfall that sank a similar effort 30 years ago, when scientists grew cells from patients’ tumors in lab dishes and tested chemotherapies on them. Unfortunately, the transplants lacked key parts of the human tumor, including the surrounding “microenvironment,” and didn’t help patients.

To get around that and other limitations, the Champions process uses good-sized bits of tumor — about as big as a pickled caper.

The tumors in the avatars retain, at least initially, the organization and support tissue of the patient’s tumor and so “are thought to more accurately represent the complex biochemical and physical interactions between the cancer cells and their microenvironment,” researchers at the British Columbia Cancer Agency wrote in 2014.

To create a PDX, cancer surgeons send pieces of a patient’s tumor, removed during surgery or biopsy, to a lab. Technicians cut the tissue into fragments and slip them under the skin, and sometimes into the corresponding organ, of mice bred to be “immunosuppressed” so they will not reject the transplant.

It typically takes Champions four months for the xenograft to take in the mice and then to be transferred to yet more mice, sometimes 20 or even 40, said Champions President Dr. Ronnie Morris.

In about one-quarter of cases, the transplant doesn’t survive and grow. If it does, the patient’s physicians instruct Champions (whose stock began trading on the NASDAQ last August) which chemo cocktail to test.

Initial testing takes a month, and if the treatment seems to be shrinking the tumor, Champions runs the test for an additional month. “You want to know: Does the tumor flip in the second month and stop responding?” Morris said.

Trouble is, “that’s time that patients with advanced cancers often don’t have,” said Dr. Warren Chow, a sarcoma expert at the City of Hope National Medical Center, who declined to participate in a Champions-sponsored trial. “It’s also a very expensive proposition.”

Champions charges $2,500 for each drug or combination tested. It is not covered by insurance.

At Dana-Farber, several of Demetri’s sarcoma patients have asked for avatars. “I tell them I don’t believe in it” for use in patients (as opposed to research), he said. “People think if they can buy this, it must be approved” by the Food and Drug Administration. But it’s not. (The test falls into a gray zone of regulation.)

In cases where patients have argued they’re going to die anyway, Demetri has relented and sent Champions a tumor sample. But there is such a “limited toolkit” of chemotherapies, he said, that the drug that works in the mice “is often what the oncologist would have done anyway.”

The clinical trials are intended to show whether avatars can do better than that. Evidence so far is limited.

A 1988 study found that mice avatars for colon, lung, stomach, and other cancers predicted human responses in 90 percent of cases. But it was too time-consuming and impractical to use for patients, Dr. Heinz-Herbert Fiebig of Germany’s University of Freiburg concluded, and the idea of personal avatars went by the wayside.

It was eventually resurrected, including by Champions Cofounder Dr. David Sidransky, a cancer biologist at Johns Hopkins University. In a 2014 study he led, pieces of sarcomas from 29 patients were implanted into mice; 22 took. Six patients died before the mice yielded treatment clues; of the remaining 16, a chemotherapy’s effect in mice jibed with its effect in 13 patients.

The scientists concluded that avatars “can guide treatment for rare tumors such as sarcomas.” But the study did not show whether patients with avatars did better than those without.

Many oncologists, therefore, remain unconvinced. Chow, a spokesman for the American Society of Clinical Oncology, said he is willing to send a tumor sample to Champions if a patient insists, but he calls avatars “a great research tool, not a viable clinical tool.”

Champions’ Morris, perhaps surprisingly, agrees.

“If you asked me, ‘Should we build a personalized PDX for every cancer patient?’ I’d say no,” he told STAT. “It’s burdensome and expensive, and patients need answers now; they don’t have two months to wait.” Champions does about 100 personal avatars per year, he said.

Morris is more optimistic about the use of avatars for research, the company’s focus, including to identify characteristics of tumors that predict response to combinations of chemotherapies. If that succeeds, then patients wouldn’t have to wait for their own personal mouse: oncologists could analyze their cancer and, based on generations of avatars, pick the treatment that’s most likely to help.

Even that modest goal faces obstacles, however. Basic principles of cancer biology cast doubt on how useful avatars can be.

Although the avatars try to preserve key characteristics of a patient’s tumor, they are far from exact duplicates. Cancer biologists have discovered recently that “support cells” around tumors affect their growth and response to treatment, for instance. But in avatars, said Demetri, “human support cells get replaced with mousy support cells, so it’s a caricature of human cancer.”

And the differences go beyond that. Growth factors, signaling molecules, immune systems — “there are a hundred other things different between xenografts and real human tumors,” said Dr. Matthew Vander Heiden, a cancer biologist at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology.

Perhaps the greatest concern is that no one knows if the avatars give false negatives, false positives, or both. A false positive (a treatment works in the mice but not the patient) subjects people to ineffective, and usually toxic, drugs. But a false negative (if an oncologist were incorrectly guided by the mouse’s nonresponse) could cause a patient to miss out on a potentially life-saving treatment.

Ford’s cancer progressed too fast for the mice to tell his doctors anything. It remains to be seen if they will ever make a difference to meaningful numbers of other patients.

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