Journal of the National Cancer Institute Advance Access originally published online on July 8, 2008
JNCI Journal of the National Cancer Institute 2008 100(14):984; doi:10.1093/jnci/djn247
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© Oxford University Press 2008.
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Man's Best Friend Is Also a Friend of Cancer Research
Dogs are no strangers to cancer research. More than 40 years ago researchers learned that cancer develops spontaneously in dogs, just as it does in humans. They also found that cancer cells viewed under the microscope look similar in dogs and humans. Now, two other developments—the completion of the sequencing of the canine genome in 2005 and the technology that has allowed scientists to look for genes and biomarkers associated with cancer—have brought dogs into the spotlight again. Several cancer studies using dogs are currently under way, and researchers hope to show that these animals can offer clues about human cancer as well.
In an article published in the Journal of Chromosome Research in February, Jaime Modiano, D.V.M., Ph.D., of the University of Minnesota in St. Paul and Matthew Breen, Ph.D., of North Carolina State University in Raleigh reported that they found the same genetic abnormalities in blood cancers of both humans and dogs.
Chronic myelogenous leukemia is marked by a certain gene translocation, which Modiano and Breen found in both species. The researchers also discovered that the genetic abnormalities found in Burkitt lymphoma and chronic lymphocytic leukemia were present in dogs as well. "You had a moment where you wanted to rub your eyes to make sure you were not seeing double," Modiano said. "It turned out to be true."
The researchers said that they will continue to search for chromosomal aberrations that are specific to certain cancers in dogs and will determine whether they are also found in humans. Identifying the functional mechanisms surrounding these genetic changes in dogs could give insight into how a particular cancer responds to a specific treatment.
Despite these findings, dogs will probably never replace mice, which are "the giants of the biomedical field," according to Peggy Tinkey, D.V.M., chair of veterinary medicine and surgery at the University of Texas M. D. Anderson Cancer Center in Houston. Laboratory researchers have a store of genetically engineered mice to choose from and can engineer cancer in mice with specific mutations or by injecting one cancer cell line into the tissue. Because these cancers are not heterogeneous, as they are in dogs and humans, scientists can target one genetic mechanism to study. Mice also serve as an early gatekeeper in determining whether a new drug is toxic.
Nonetheless, dogs offer some advantages. "There are specific questions in human cancer development that a dog can help answer," said Chand Khanna, D.V.M., Ph.D., director of the comparative oncology program at the National Cancer Institute. Dogs can help illuminate environmental causes of cancer in humans that, along with age and nutrition, influence cancer development in both species. Also, some breeds are more susceptible to certain cancers, making them a more consistent model. Golden retrievers, for example, have a one-in-eight chance of getting lymphoma, compared with other breeds that have a one-in-15 chance. In the testing of new treatments, the dog's size, anatomy, and physiology are more similar to humans than rodents. And dogs and humans have genetically complex tumors, forming a mosaic of cells in which different genes are activated. According to Khanna, this cell cocktail adds to a tumor's resistance to therapy and its tendency to metastasize.
Khanna's comparative oncology program at NCI, launched in 2003, is a collaboration between veterinary and human oncologists who plan their research with each other in mind. It runs dog clinical trials with new drugs, testing efficacy and helping to establish doses and regimens. "Dog trials can offer a focus that adds a basis or starting point to design the next human study," Khanna said.
In a recent dog trial sponsored by the program, scientists delivered human tumor necrosis factor, which kills cancer cells, to tumor cells while avoiding healthy tissue by targeting a specific integrin protein. Another study looked at rapamycin, which suppresses the immune system for human organ transplant patients but also has anticancer properties. The study sought to find the dose at which the drug's benefits outweighed the harms caused by immunosuppression. Results of both studies are in review for publication. Future dog studies, Khanna said, may look at rapamycin combined with other drugs in treating cancer.
In other studies, researchers are using dogs to track a drug's response. A study led by David Vail, D.V.M., at the University of Wisconsin in Madison looked at a lymphoma drug that blocks cell division and must be activated in white blood cells through an enzymatic reaction. Mice don’t have these enzymes, but by using dogs, the researchers could monitor the active drug in normal white blood cells.
"We’re at a period of time where the microscope is being turned on this model," Vail said. "The next 5 or 10 years will prove or disprove [our theory that] the treatment of cancer in companion animals is applicable to people."
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