From pets, clues to human cancer
They can sit, and stay, and fetch. They can sniff out drugs, guide the blind, dial 911.
Maybe they can even cure cancer -- or help cure it, anyway. Many scientists see cancer in dogs as an excellent model for cancer in humans, and evidence is growing that they’re barking up a very useful tree.
Late last month, a vaccine to treat canine melanoma won conditional approval from the U.S. Department of Agriculture -- the first time the government has approved a therapeutic vaccine for treating cancer in either animals or people. And trials are underway on a similar vaccine to treat melanoma in people.
“Now we know it’s really possible,” says Dr. George Demetri, director of the Ludwig Center at the Dana-Farber/Harvard Cancer Center in Boston. “If we can do it in dogs, just give us time, and we can do it in people.”
The new vaccine is just one of many examples where studying cancer in dogs is paying off not only for the dogs -- millions of whom develop cancer every year -- but also for human beings.
Three years ago, the National Cancer Institute established a Comparative Oncology Program to promote cross-fertilization between dog and human cancer studies. More and more researchers are coming to see value in this approach.
“Before, it never really crossed my mind to enroll pets as research subjects,” says Dr. Jedd Wolchok, assistant attending physician at Memorial Sloan-Kettering Cancer Center in New York -- and one of the lead investigators in the project that developed the canine melanoma vaccine.
“He’s my police partner, and he’s my family’s best friend,” says Officer Mike Serio of the Salt Lake City Police Department, referring to his 10-year-old bloodhound, JJ, who was diagnosed with melanoma in his mouth in January.
Four round-trip flights to New York later, Serio is waiting to see if JJ is responding well to the melanoma vaccine, which should be available from veterinary oncologists across the country in a few months.
The vaccine is the result of 6 1/2 years of studies in dogs with melanoma by a team at the Animal Medical Center in New York and a team at the Sloan-Kettering Institute, a few blocks away.
The studies began with a conversation between human doctor Wolchok and animal doctor Philip Bergman, head of the Donaldson-Atwood Cancer Clinic & Flaherty Comparative Oncology Laboratory at the Animal Medical Center.
“We shared our frustration with trying to treat melanoma, him in dogs and me in people,” Wolchok says.
The idea for the studies originated when a student in a lab at Sloan-Kettering tried to immunize a mouse against melanoma using human melanoma cells. It worked. The mouse’s immune system mounted a reaction against the human cancer cells because they were from another species. At the same time, it immunized itself against melanoma cells of its own -- since mouse and human melanomas share similar properties.
It is what’s called a xenogeneic vaccine -- one that introduces biological material from one species into another.
Bergman and Wolchok tested the vaccine in dogs that had developed melanomas, and in 2003, reported dramatic success. Median survival for the nine dogs that got the vaccine was more than a year, three times as long as dogs are known to survive with conventional therapies. Some dogs survived much longer than the median.
That success helped pave the way two years ago for the start of human trials, in which subjects are being given mouse melanoma cell DNA. Five small studies with about 20 subjects each are ongoing, primarily designed to test safety.
Many human cancer vaccines are under development: Their aim is to boost the ability of the sick person’s immune system to fight the disease. But the dog melanoma vaccine is the first such cancer vaccine to get government approval.
There are many other examples of the cross-pollination between dog cancer research and human cancer research. For example, a new type of radiation therapy delivery -- a marriage of CT scanner and linear accelerator -- was first tested on dogs with sinus cancer by a team led by Dr. Lisa Forrest, a professor of oncology at the University of Wisconsin’s School of Veterinary Medicine.
Conventional radiation can destroy sinus tumors, but it’s not precise enough to avoid the eyes, so it usually makes dogs go blind. The new radiation machine successfully pinpointed the tumors, and now, marketed as TomoTherapy, it’s being used to treat humans at hospitals around the country, including the L.A. area.
Another useful dog-human match-up arose in treating osteosarcoma, the most common type of bone cancer. Dr. Stephen Withrow, director of the Colorado State University Animal Cancer Center, sees about a dozen dogs a month with this cancer. Dr. Ross Wilkins, medical director of the Denver Clinic for Extremities at Risk, sees two or three children a month with the human version.
Over years of collaboration, the two have developed a protocol for treatment combining chemotherapy and surgery that leads to a survival rate in children of more than 90%, and similar success in dogs. Survival rates for children with conventional treatments can be down around 50%.
Still more good news for people arose out of dog studies on mast cell tumors -- cancers common in dogs, not in people. In a study of these tumors, Dr. Cheryl London, an associate professor of veterinary biosciences at Ohio State University, found that a drug called SU11654 inhibits a gene found in a variety of human cancers.
The drug company Pfizer confirmed these findings for SU11654 and a related drug, SU11248, both of which the company owns. SU11248 was approved last year to treat two kinds of human cancer, one in the kidneys and one in the stomach and intestines. It is now sold as Sutent.
Last year, researchers had another cross-species success with a therapy to stop the growth of new blood vessels to feed a tumor. The success came, in dog trials, only after researchers extended the evaluation period. Because of what happened with dogs, the evaluation period was also extended in human trials, says Dr. Melissa Paoloni, a veterinary oncologist at the National Cancer Institute.
“Previously, human patients would have been taken off trial by then,” she says -- before the treatment had time to work.
With the establishment of the Comparative Oncology Program at the National Cancer Institute, the study of cancer in dogs will broaden, says the institute’s Chand Khanna, who heads the program. The institute is trying to spread the word that natural cancers in dogs are a fruitful way to learn more about cancer causes and therapies.
The program has established a consortium to collect tumor tissue, DNA and blood samples from dogs. Scientists from around North America will be able to submit proposals for how they believe they could put specimens from it to good use. It has also established a network of 14 veterinary schools across the country that have signed on to conduct clinical trials in collaboration with the cancer institute and the pharmaceutical industry. This consortium recently completed its first trial, and its second and third are just getting underway.
There are obvious reasons why studying cancer in pet dogs makes sense, proponents say. For one thing, people love their dogs and want to save them if they get sick. Sometimes, enrolling the dog in a trial may be its only hope. (Every dog used in a trial is a pet with cancer whose owner has entered the trial voluntarily. Often owners don’t have to pay for the experimental treatments.)
But there are other, less sentimental reasons why canine cancer research seems so promising.
“These are patients much bigger than a mouse that develop tumors on their own, not like tumors in mice that we inject.” Dr. Steven Libutti, surgical oncologist at the National Cancer Institute.
Dogs and people also share the same environment -- and therefore confront many of the same risks. Also, the cancers that both species develop spontaneously are often nearly identical in their biology, behavior and response to conventional treatments.
There are differences, of course: Some of the major cancers in people -- lung, breast, prostate -- are not big problems in dogs, the latter two primarily because so many dogs are spayed or neutered. (Those cancers are common in Europe where altering procedures are not.)
Likewise, some of the most widespread cancers in dogs -- osteosarcoma, melanoma, lymphoma -- are rarer in people. But this turns out to be useful. Whereas it can be hard to find enough subjects for big clinical trials in people with these cancers, it’s all too easy to find enough dogs.
Purebred dogs provide another valuable research opportunity, especially now that the entire dog genome has been sequenced, says Dr. Niels Pedersen, director of the Veterinary Genetics Laboratory in the School of Veterinary Medicine at UC Davis. Breeds develop cancers at different rates, and scientists can use this fact to find genes involved in a specific type of cancer.
Other advantages for studying dogs are simply logistical. Because dogs are relatively large, machines used on people -- e.g., MRIs and CT scans -- can also be used on them. And follow-up biopsies to judge the effectiveness of a procedure are often possible in dogs when they might not be in people.
Dogs have shorter life spans than people, and their cancers move faster. But this sad fact turns out to have one saving grace. Studies of dogs can be completed -- and their results known and, hopefully, put into practice -- in much less time than studies of humans.
Many researchers report that owners whose pets are enrolled in trials often feel good about the part their pets may play in advancing science. Even if their own dogs don’t do well, they know that researchers could learn something that might someday help someone else’s dog -- or child.
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In studies, cats are ‘more tricky’ than dogs
Most cancer research on four-legged patients is being done on dogs. Why not pet cats? Aren’t they up to scratch?
Cats do share many of the attributes that make dogs so useful, and it’s not as if they’ve never lifted a paw to help medical science: Development of the feline leukemia vaccine in the 1980s, for example, helped advance research on human diseases such as AIDS and cancer.
But, in general, dogs give more reliable data, says Dr. Jay Stone, a veterinary oncologist at Santa Cruz Veterinary Hospital in Santa Cruz. “Cats are a little more tricky and unpredictable,” he says.
For one thing, although dogs react differently to drugs than humans do, drug reactions in cats can be even more dissimilar. (Tylenol, for example, can kill cats.)
For another, feline tumors can sometimes go away spontaneously, without any treatment. In a trial testing whether a treatment works, this could give falsely encouraging results.
-- Karen Ravn
