A Better Mousetrap

The traditional means of testing a potential treatment for cancer is to get a lab full of mice and conduct controlled experiments that attempt to prevent tumor growth. In the late 1990s, such studies produced a new medication that choked off the blood flow to malignant cells. It was hailed as a wonder drug. “There was literally a headline in the New York Times saying scientists would cure cancer within two years,” says Elizabeth McNiel, a veterinary oncologist at the Cummings School of Veterinary Medicine. “It was huge.”

But once researchers tested the drug outside the lab, in human clinical trials, it did not produce such miraculous results. Drugs that cut off blood supply to tumors “have been disappointing [in treating] many types of cancer,” says McNiel. “There seems to be a really big disconnect between what we observed in the mouse and what was observed in humans.”

In what could signal a new direction for cancer research, McNiel hopes to bridge that disconnect by studying the disease in cats. The work could produce breakthroughs to advance cancer treatment in cats and humans.

As companion animals, cats live in the same environments as their owners, and the cancers they develop tend to occur in similar ways to those in humans. Whereas mouse cancers usually are small and contained, feline cancers come in various sizes and spread throughout the body.

“We think that [human and feline cancers] may be parallel in their underlying causes,” says McNiel. Studying cancer in domestic cats may produce more reliable results than using lab mice and could result in more effective treatments in the long run.

McNiel studies squamous cell carcinoma, a cancer of the mouth typically caused in humans by tobacco use, though increasingly by human papillomavirus (HPV). It is also one of the most common feline cancers. Squamous cell carcinoma is usually quite aggressive in people and animals, metastasizing quickly and resisting traditional treatments. “We’ve treated these cats with surgery. We’ve treated them with radiation, and the average survival time is just a few months,” says McNiel.

Those grim statistics make this cancer a good candidate for study in a clinical environment, McNiel says, because pet owners might be more willing to consider a nontraditional therapy when faced with such dismal survival rates.

In research funded by the Morris Animal Foundation, McNiel is investigating the potential of a drug used to treat human cancer. The designer peptide called Anginex contains 33 amino acids that bind to another protein in the blood vessels that supply tumors with growth-promoting nutrients and oxygen. The bound drug helps switch off the flow of blood to the tumor cells, essentially severing their lifeline.

Thus far, McNiel and her colleagues have conducted successful safety trials to ensure that the drug won’t harm cats—a necessary first step in research with pets. They tested the drug in the laboratory, using feline blood vessel tissue, as well as in a dozen cats being treated for squamous cell carcinoma at the Foster Hospital for Small Animals at Tufts.

Now the researchers are preparing for a larger study, in which 25 cats will receive the drug to determine whether it does indeed shrink their tumors. Unlike large clinical trials where several hundred animals might be treated to statistically prove the effectiveness of a particular drug, this small-scale study is more qualitative, examining how the drug works and how it might be developed further, McNiel says.

“We know these therapies have not been very successful in humans, and we have some ideas about things that might be barriers to success,” she says. It could be, for example, that simply choking off the blood supply negates the ability of other treatments, such as chemotherapy, to reach tumors, thereby actually encouraging them to spread. “This larger study is not to show that this treatment is superior to another treatment,” McNiel says. “It’s really to try and understand the biology of what this treatment actually does.”

One possibility is administering the drug in concert with other therapies, such as radiation or chemotherapy, potentially augmenting their combined ability to fight the disease.

Another avenue McNiel is exploring is to reverse the drug’s function to actually improve blood flow to the tumor. While that might sound counterintuitive, it could, for example, make chemotherapy more effective by allowing more chemicals to attack the tumor. Once the initial studies are done, McNiel says, the researchers can move on to research that would use Anginex in addition to conventional treatments.

This article first appeared in the Winter 2013 issue of Tufts Veterinary Medicine magazine.

Michael Blanding is a freelance writer in Brookline, Mass.