Friday, September 30, 2016

Four-legged Fighters

By Catherine O'Neill Grace

How our pets are helping us win the war on cancer

Gloria Riccobono, along with Leo and Hannah

Gloria Riccobono shares a moment with Leo and Hannah, right, who was undergoing cancer treatment at the Cummings School. Photo: Alonso Nichols

Gloria Riccobono’s two standard poodles—Hannah, a chocolate female, and Leo, an apricot male—were anything but pampered. The athletic dogs have led an active outdoor life, often accompanying their owner on strenuous hikes. Then last winter, as Riccobono and the dogs were heading down a trail, it became clear that Hannah wasn’t her usual stalwart self.

“At the end of the hike I noticed that she stumbled,” Riccobono says, “and when we got home and she was resting on her bed, she was kind of swaying. I knew something was not right.”

Unfortunately, Riccobono’s instincts about her 10-year-old dog, which she has had since puppyhood, were correct. Hannah was diagnosed with lymphoma, a cancer that attacks lymph nodes throughout the body.

Each year, some six million of the 65 million dogs in the United States will be diagnosed with cancer, according to the National Cancer Institute. Of the nation’s 32 million cats, six million come down with cancer each year. On the human front, more than 11 million Americans are living with cancer, according to the American Cancer Society, and more than one million new diagnoses are made each year.

Dogs and humans have more in common than you might think. They often contract the same types of cancers: prostate, lung, head and neck cancers, breast cancers, soft tissue sarcomas, melanoma and the bone cancer osteosarcoma.

Studying animals with cancer in the context of how people get the disease and respond to treatment is an emerging discipline called comparative oncology. It is a field that could mean success for Cancer 2015, the National Cancer Institute’s challenge to researchers to “understand the disease and create interventions so that no one will suffer and die prematurely from cancer” within five years.

Comparative oncology has mobilized veterinary and medical oncologists, the pharmaceutical industry and academic centers involved in cancer research, including the Harrington Oncology Program at the Cummings School of Veterinary Medicine.

The sequencing of the canine genome in 2005 by scientists at the Broad Institute of Harvard and MIT has only heightened interest in the potential of comparative oncology. DNA mapping has shown that dogs and humans are more genetically similar than humans and rodents, making dogs better models than laboratory mice and rats for studying how tumors develop. Previously, the bulk of cancer research had been done with rodents, and when it came time to test results in human clinical trials, the research often didn’t translate well.

A Two-way Street for Understanding

“We have known for a long time that many canine tumors are good models for studying human cancers,” says John Berg, a cancer surgeon who chairs the department of clinical sciences at the Cummings School. “The cancers present in similar ways, and they respond similarly to treatment.”

At Tufts, veterinarians are collaborating with oncologists at Massachusetts General Hospital to gain insights into osteosarcoma, the most common bone malignancy in humans. The disease, which usually develops during the growth spurts of adolescence, occurs most often in teenage boys. In humans, osteosarcoma invades the long bones of the body—above or below the knee, or the upper arm, near the shoulder. In dogs, it usually occurs in the forelimb.

“We have a better understanding of cancer, including osteosarcoma, because of the work we have done with animals,” says Lisa G. Barber, a veterinary oncologist at the Cummings School. “Cancer in the weight-bearing bones is more prevalent in dogs than in people,” she says, noting that limb-saving surgeries now used to treat children with the disease were first developed in dogs.

Cancer treatment in animals and humans “is a two-way street,” says Kristine Burgess, V97, a veterinary oncologist at Tufts. “We use humans as our lab rats, too. We study the human cancer literature and use the same chemotherapy agents and protocols that are employed to treat humans with cancer.”

Because comparative oncology is a young field, Burgess says, “people often don’t understand that animals get cancer with the same or similar frequency as humans, and that we actually treat animals with the standard human treatments: surgery, chemotherapy and radiation therapy. We don’t just euthanize them.”

Veterinary oncologists study spontaneously occurring cancers in animals—those that arise from the same environmental and genetic reasons that human cancers do. And like humans, dogs today are living longer, meaning that more of them—and more of us—will develop tumors.

According to the National Cancer Institute, people ages 65 and older are 10 times more likely to develop cancer than younger people, and the mortality rate for older cancer patients is 16 times greater than that for younger patients. In animals, cancer kills nearly half of dogs and cats over the age of 10, according to the American Veterinary Medical Association.

Comparative oncologists are working on three fronts in the war on cancer: understanding environmental risk factors such as exposure to herbicides, pesticides and tobacco smoke, unraveling cancer’s genetic footprints and developing new treatments.

Canine and human cancers share similar gene expression and molecular alterations, Burgess says. “The way they appear under the microscope, their genetic composition, all of that can be similar. But what makes it the best comparative model is that dogs have similar body systems to humans.”

Barbara Davis, a veterinary pathologist at the Cummings School, is leading studies to determine how common environmental chemicals may cause cancer in dogs. Companion animals share our homes, she says, and so they provide a unique opportunity to help us understand gene-environment interactions that may lead to cancer.

Because dogs have shorter life spans than humans, their cancers progress more rapidly, and veterinarians can figure out more quickly which treatments work and which don’t. That gives researchers an opportunity to gather data about cancer progression in a much shorter time.

“A dog’s life is not as short as that of a mouse,” says Burgess. “It’s more analogous to what you’re going to get in a human. A dog can be that canary in the coal mine.”

Cats and Cancer

Cats, like dogs and people, develop cancers of the breast, colon and lung, as well as lymphoma and leukemia. In the late 1970s, Tufts faculty member Susan M. Cotter, an internationally known researcher in veterinary clinical oncology, conducted pioneering investigations of the feline leukemia virus (FeLV) with researchers at the Harvard School of Public Health.

Her work was the first to demonstrate that viruses that cause leukemia and other neoplastic diseases—those that involve the abnormal growth of cells—can be contagious. Cotter’s findings produced some of the best early descriptions of the response of feline and canine lymphoma to chemotherapy and stimulated a surge in clinical research on the use of chemotherapy for treating cancer in animals.

For reasons that are not fully understood, feline cancers tend to be more aggressive, and so may not respond to treatment as easily as canine cancers. Another challenge is that feline cancer symptoms are more subtle. “They tend to present in late stages,” says Barber, the veterinary oncologist. Even though a cat may appear healthy, she says, it may be harboring a cancer that, if detected early enough, can be treated.

Cats can get very aggressive mammary tumors that almost always metastasize, spreading to other organs. “These tumors resemble highly malignant breast cancers in people, so they’re a good model for us to study,” says Barber. Spaying dogs before their first heat almost always eliminates the risk for developing breast cancers, she says. The effect of spaying cats is less clear, she says, even though cats that are not spayed are more likely to develop mammary cancer.

To avoid some of the environmental risk factors for cancer, Barber suggests that pet owners avoid smoking indoors and get their homes tested for radon gas. “We don’t have good preventive strategies for cancer in animals yet,” she says. “Early detection is one of the things that can make a difference in the outcome.”

As with human cancers, the options for treating canine and feline cancers include surgery, chemotherapy and/or radiation, depending on the type of tumor.

The prospect of chemotherapy is anxiety-producing for many pet owners, Burgess says, because of what they know about the nasty side effects of the treatment in humans. But chemo for dogs generally involves fewer and shorter rounds of treatment and lower doses of the powerful drugs.

“People will say, ‘Oh, my Aunt Edna had chemo, and I can’t do that to my pet,’ ” Burgess says. But only non-shedding dogs will temporarily lose their hair, and most will lose little or no fur. And in reality, less than a third of canine cancer patients experience unpleasant side effects, and fewer than five percent get what Burgess calls “human-style sick.”

As in human medicine, research into new and better treatments for animal cancer is ongoing. Albert Ahn, V89, V94, president of AB Science, in Short Hills, N.J., reports that his company is seeking FDA approval for the drug masitinib, which has shown promise in treating mast cell tumors, a common skin cancer in dogs.

The drug, administered orally as a pill, is not as toxic as commonly used chemotherapies, and it targets a tumor’s molecular structure, destroying or disabling diseased cells or tissues. More than a dozen treatments that target tumor biology have been approved for human cancers, but masitinib—already used in Europe—would be among the first such veterinary therapies approved in the United States. The drug could allow veterinarians to prescribe long-term, maintenance doses to stabilize tumors rather than subjecting an animal to more invasive surgical solutions or chemotherapy.

The goal of any type of veterinary cancer treatment, Burgess says, is not necessarily to cure, but to make the animal comfortable and preserve its regular routine and the bond between animal and owner for as long as possible.

“Quality of life is our main goal, always,” she says. “Fortunately, the majority of cancer patients and their owners continue to enjoy time together. For animals, because their life span is limited, if you can extend their lives for up to a year or more, that’s a long time.”

Knowledge and Compassion

When Hannah, Gloria Riccobono’s standard poodle, began her chemotherapy at the Cummings School, things didn’t go well at first. The dog was anxious. “Hannah has never been away from Leo, her litter mate,” she says. “They’re like two little old people. She follows him everywhere he goes. So the next time we went to the hospital, I brought him with her. Things went much better for her because he was nearby.”

The hospital staff allowed Leo to stay with Hannah as she received her treatments. “As long as Leo’s there, she’s happy,” Riccobono says.

Hannah’s advanced lymphoma went into remission after her first round of treatment, and she experienced some happy months. “She had a good summer,” says Riccobono.

Although Hannah’s cancer has returned and metastasized and she is receiving another round of chemotherapy, Riccobono says she would not have done anything differently.

“I feel like I’m on the cutting edge by being here at Cummings with my dog,” she says. “There is so much knowledge and so much compassion. I know they are doing everything they possibly can.”

This story first appeared in the Spring 2010 Tufts Veterinary Medicine magazine.

Posted August 10, 2010