Article written by Amy Dockser Marcus
Man’s Best Friend
Why dogs are studied for human cancer research:
•Dogs have strong genetic similarities to people. They also get naturally occurring cancers.
•There are similarities in the types of cancers that develop. Dogs respond to chemotherapy much like people do.
•The canine genome has been sequenced, allowing scientists to study what gene mutations are linked to specific cancers.
•Faster disease progression in dogs means researchers can see more quickly what drugs work.
Source: National Cancer Institute
Researchers hoping to develop a promising new approach to treating cancer in people are trying it in another group: pet dogs.
The aim of personalized medicine is to design an optimum cancer therapy after analyzing genes in a patient’s tumor. Dogs, which have strong genetic similarities with humans, get many of the same types of cancers as people and have similar responses to cancer-fighting drugs. When diagnosed, dogs often have a shorter survival time than humans, allowing researchers to see if a drug is making a difference in a shorter period.
In people, it can take three to five years from the time they are diagnosed until the disease reaches an advanced stage. But in dogs, trials testing whether novel drug therapies extend survival can be finished in six to 18 months, says Melissa Paoloni, director of the Comparative Oncology Trials Consortium at the National Cancer Institute.
Within a week, nearly 300 pet owners responded with an offer to send saliva samples to be analyzed. That kind of large and speedy response in a human study is very difficult to achieve, says Jeffrey Trent, who organized the pet study. Dr. Trent is president and research director at Translational Genomics Research Institute in Phoenix, which is participating in a privately funded effort to develop personalized treatments for people with certain types of melanoma. If the personalized medicine approach “makes a difference in treating the canines,” Dr. Trent says, “it can readily be moved into trial in humans.”
All cancers are believed to have genetic features, though what particular mutation or other aberration is involved with each type of tumor often isn’t known. When this information is discovered, through genetic sequencing, for example, tests can be done to see if the tumor responds to any of various drugs or combinations of drugs.
People and dogs get many of the same types of cancers. Here are some they share:
•Osteosarcoma, a bone cancer
•Non-Hodgkin’s lymphoma, a blood cancer
•Glioma, a brain cancer
•Melanoma, a skin cancer
•Head and neck carcinoma
•Soft tissue sarcoma, a cancer of tissues such as muscles
Source: National Cancer Institute
Although the cost of sequencing a genome has plummeted, it is still expensive and therefore not readily available to the vast majority of patients. And, in line with accepted standards of care, new agents are traditionally tried only in people who have advanced disease or have failed to respond to traditional therapies. With dogs, drugs and different drug combinations can be tried in newly diagnosed animals.
The use of so-called targeted therapies to treat some cancers is considered an early form of personalized medicine. For example, women with a certain kind of breast cancer in which testing shows the Her2 gene is over-expressed are given the drug Herceptin. Last year, the Food and Drug Administration approved a drug to treat patients whose melanoma tumors express a BRAF gene mutation.
One question researchers face is whether a patient’s tumor can be analyzed, and a treatment recommendation formulated, quickly enough to allow doctors to make clinical decisions. Working with dogs, Dr. Paoloni and colleagues conducted a pilot study last year to see if they could accomplish this in less than a week. The researchers enrolled 31 dogs with different types of cancer, including lymphoma and melanoma. The result: A genetic analysis of each dog’s cancer and a report listing which chemotherapy agents might best treat it, was generated for each dog in under five days, a “feasible” time frame for treatment, says Dr. Paoloni.
Researchers, including those at the National Cancer Institute, plan to launch three clinical trials later this year in dogs with osteosarcoma, a bone cancer, angiosarcoma, a blood-vessel cancer, and melanoma, the deadly skin cancer. The trials will test combinations of medicines based on the genetics of the dogs’ tumors. They also will try to analyze whether drug regimens based on personalized tumor data can prevent cancer from spreading to other organs and lead to longer survival.
The researchers say they believe that trying to understand how to stop metastasis in dogs’ cancer will offer insights into the process in human cancers as well.
Stephen Gately heads a group at Translational Genomics that is setting up clinical trials on personalized medicine for people. Dr. Gately wanted his dog, Bob, to benefit from the approach after the pet got cancer last year. Working with colleagues, he had a biopsy from the dog’s cancer in one of his lymph nodes analyzed for genetic information.
It took a while for Dr. Gately to realize that Bob, a Bernese Mountain Dog, was sick. “Dogs with cancer are very good at covering up when they are not feeling well,” the Scottsdale, Ariz., resident says. But one day, Bob came in from outdoors coughing and seemed to have difficulty breathing. The vet found enlarged lymph nodes in Bob’s neck and a biopsy revealed he had lymphosarcoma, an aggressive form of lymphoma that is prevalent in dogs.
Bob was treated with the same drugs humans get for lymphoma. The pet’s disease progressed so rapidly, however, that after a family celebration at Christmas time, they decided to put the dog to sleep. He was never enrolled in a formal personalized medicine trial.
“I know we can do better than the old drugs,” says Dr. Gately. Bob’s data are being studied at the institute and will be used to help develop future personalized-medicine trials, Dr. Gately says.