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Dogs Shed New Light on Cancer Genes in Humans

March 15, 2007 at 6:40 PM EST
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BETTY ANN BOWSER, NewsHour Correspondent: After all of the poofing, coifing, spraying and prancing, the purebred dogs that compete at the Annual Westminster Kennel Club’s Dog Show in New York aren’t just the best examples of their breeds.

Scientists now believe they may be best at something else: providing answers about why humans get cancer.

It’s estimated that, every year in the United States, 10 percent of all dogs develop some form cancer, and purebreds like these are perfect for research because their genetic make-up and controlled lineage is clearly traceable. Champion Irish wolfhounds, like Greta, are leading the way.

Backstage, researcher Dana Mosher from the National Institutes of Health swabbed Greta’s mouth for DNA.

DANA MOSHER, National Human Genome Research Institute: The purebred domestic dogs, in order to be a registered member of the club, both of those dogs’ parents had to have been registered members, and their parents, and their parents. So the genetic pool for a particular breed is very, very small.

So what you’re hoping is that most of their DNA looks similar and that it’s easier to find that area where they look different and that is associated with the disease of interest.

BETTY ANN BOWSER: Greta’s DNA went to the National Human Genome Research Institute in Bethesda, Maryland, where scientists isolate the genes that cause cancer. Dr. Elaine Ostrander heads the program.

ELAINE OSTRANDER, National Human Genome Research Institute: Most of the cancers that are a problem in humans, we see in dogs. So, melanomas, skin cancers, lymphomas, leukemias, most of the things we think about in humans we see as canine cancers, as well.

We want to identify the genes that are responsible for those diseases in dogs. And, in doing so, we’ve learned a lot, almost certainly about what’s responsible for those diseases in humans, as well.

BETTY ANN BOWSER: Different kinds of dogs are susceptible to different forms of cancer, so their breeders are highly motivated to help with the research.

ANNE MARIE KUBACZ, Dog Breeder: I think that that’s one of the responsibilities of breeding a good dog, is recognizing what kinds of problems your breed can have.

BETTY ANN BOWSER: Anne Marie Kubacz not only breeds champion Irish wolfhounds, she also shows champion Irish setters, like Spencer. Both breeds are susceptible to bone cancer. Kubacz hopes that research will mean that eventually she can breed dogs without that inherited trait.

ELAINE OSTRANDER: Once we find what that gene is that’s messed up, then it becomes very, very quick to figure out how to develop targeted therapies to overcome that in the cell for humans, as well as for dogs.

Comparative oncology

BETTY ANN BOWSER: It's all part of a growing field of work called comparative oncology, one that should help dogs and humans.

DR. JAIME MODIANO, Veterinarian, University of Colorado: This is a tumor from one of our dogs in our study. And you can see that we've taken a section of the tumor out.

BETTY ANN BOWSER: Jaime Modiano is looking at cancer tumors to better understand the role genes play in their growth. The veterinarian and immunologist at the University of Colorado says scientists have turned to dogs because it has been difficult to find specific cancer-risk genes in people.

DR. JAIME MODIANO: How do you group humans into breeds, right? We are not breeds. My ancestry is from the Mediterranean, and Eastern Europe, and Mexico, and so what breed do I belong to? It's very hard to pinpoint that in any one of us.

But the dogs, it's a very pure sample. So by focusing on multiple breeds, we get multiple risk individual factors for a variety of different tumors that then allow us to go back and say, "OK, this is the profile of risk."

BETTY ANN BOWSER: He has teamed up with the Animal Cancer Center at Colorado State University in Fort Collins. Dr. Susan Lana, a veterinary oncologist at the center, says there's another reason dogs are a natural model for research.

DR. SUSAN LANA, Veterinary Oncologist, Colorado State University: They're in our environment. They share our household; they share the air they breathe; they share the water we drink.

These patients get their tumors spontaneously. We don't give them the cancer; it just arises. So in that sense, it mimics what humans undergo, where their cancer arises spontaneously, too.

In many mice or rodent models, the cancer is given to the patient and then they grow, and it's not necessarily a natural model.

BETTY ANN BOWSER: Lana says animal lovers have welcomed canine research, since the cancers are naturally occurring, not manufactured in the animals. The Fort Collins cancer center is taking the next step in canine research: treating dogs, like this Rottweiler named Jezebel, with new therapies.

Jezebel has osteosarcoma -- bone cancer -- and now receives injections meant to boost her immune system. Dr. Lana says using dogs as research subjects brings faster results.

DR. SUSAN LANA: Dogs' life spans are shorter than humans. We can sometimes get answers to some of the questions, like is this approach effective? Is this combination of therapy effective? We're helping the animal patient, but we're also answering some of these preliminary questions into how these medicines or these treatments might translate into human care.

BETTY ANN BOWSER: And since one dog year is equal to seven human years, early conclusions from a successful canine treatment could prompt similar treatments in humans, adding years of life to people with cancer.

DR. SUSAN LANA: Well, a dog with osteosarcoma, from the time of diagnosis with treatment, might have a life span of about a year. A human with that similar disease is going to have a life span with treatment of many, many years.

Testing vaccine in humans

BETTY ANN BOWSER: That certainly is the hope for Ken Lipmann. Lipmann volunteered for an innovative cancer vaccine at Memorial Sloan-Kettering Cancer Center in New York, a treatment that has been already proved highly successful in dogs. It's called a vaccine because it's meant to trigger the immune system to attack any reoccurrence of the cancer.

Four years ago, Lipmann was diagnosed with advanced melanoma, an aggressive skin cancer that can be fatal to both humans and dogs alike. Dr. Jedd Wolchok developed the treatment.

DR. JEDD WOLCHOK, Memorial Sloan-Kettering Cancer Center: We believe that the immune system can be trained to recognize cancer as being something foreign and dangerous.

BETTY ANN BOWSER: It's still too early to determine the results in humans. However, just down the street, at New York's world-famous Animal Medical Center, the same vaccine has wowed veterinarians with its success.

Dr. Philip Bergman is the head of oncology.

DR. PHILIP BERGMAN, Veterinarian, The Animal Medical Center: Over and over again, where we should be losing these patients early on due to spread, and they continue to be with us two, three, four, or five years out. You know, it's pretty remarkable to us.

BETTY ANN BOWSER: In both dogs and humans, the vaccine is injected after all melanoma has been surgically removed, but the patient is still at a high risk of occurrence.

DR. PHILIP BERGMAN: Over time, they've sort of come to see us as a bridge between all the mouse work that they do at Sloan-Kettering and other places to then making the jump to people.

BETTY ANN BOWSER: So far, Ken Lipmann's CAT scans shows he is clear of cancer.

DR. JEDD WOLCHOK: What I tell him each time I see him is that, every month that goes by, he has a lower risk of the melanoma coming back. So the fact that he's done this well for this long is very promising.

A 'win-win for the dogs'

BETTY ANN BOWSER: Candy is one of more than 350 dogs that have received the vaccine. Most have lived more than three years, when their life expectancy was originally only a few months.

The vaccine has worked so well that the U.S. Department of Agriculture is about to license it for dogs. Remarkably, the idea to try the vaccine on dogs unfolded almost by chance.

DR. PHILIP BERGMAN: Dr. Wolchok was introduced to me. We were at a dinner, and he literally said, you know, "Do dogs get melanoma?"

DR. JEDD WOLCHOK: I saw the opportunity to possibly, in my wildest dreams, help his dogs, but also get some early evidence for safety and efficacy of our vaccine.

DR. PHILIP BERGMAN: Four months later, we were starting a trial in dogs, the original trial, back in 2000.

BETTY ANN BOWSER: Even though it's too early to know how the vaccine will work in large numbers of people, scientists like Dr. Jedd Wolchok are rethinking the meaning of the old phrase "a man's best friend."

DR. JEDD WOLCHOK: I see them as contributing to our mission here. And I also see them as creatures living in this environment that get cancer, that get the same disease that I'm trying to help my patients with, and deserve every chance to get well.

BETTY ANN BOWSER: And patient Lipmann agrees.

KEN LIPMANN, Patient: It's been a win-win for the dogs. I'm hoping it's going to be a win-win for this old dog.

BETTY ANN BOWSER: To date, the Human Genome Institute has collected over 10,000 canine DNA samples.