Illinois Team at Forefront in Fight Against Cancer
by Kelly Coleman

Veterinary oncologists are hard to come by. Training programs, which can take as long as seven years post-DVM, are few and far between. Once an oncologist is ready to join the work force, the lure of high salaries and urban locations in the private sector make it difficult to secure faculty oncologists.

Illinois is lucky indeed to have an oncological "dynamic duo" with the partnership between medical oncologist Barbara Kitchell and surgical oncologist Nicole Ehrhart. The two combine their clinical practice and teaching with research that is attacking cancer on several fronts and making advances for both human and animal medicine. Their efforts and success in the research sector make the College's Veterinary Cancer Care Clinic rank among the veterinary elite, according to Dr. Kitchell.

The College's cancer program draws on a broad arsenal that includes traditional surgery, chemotherapy, and radiation as well as new approaches such as cytostatic therapy, immunotherapy, and gene-based diagnostics.

Here are most of the clinicians, diagnosticians, technicians, and researchers on the oncology team: front, from left, Dr. Cathy Greenfield, Dr. Nicole Ehrhart, Nancy George, Dr. Joanne Messick, Kismet the dog, Jennifer Rose; back, from left, Dr. Joseph Impellizari, Dr. Curt Daly, Dr. Monika Haefner, Dr. Timothy Fan, Shari Poruba, Dr. Barbara Kitchell, Dr. Louis-Phillipe deLorimier, Dr. Pamela Jones, Dr. Matt Wallig, Heather Soder, Dr. Sara Ayres, Char Werts, Dr. David Lurie, and Dr. John Hintermeister.

Cytostatic Therapy Holds Promise
"In the clinic, we are a chemotherapy trial center and we are a translational modeling center," says Dr. Kitchell. The purpose of a translational modeling center is to prove principles of therapeutic concepts developed in the research laboratory and pass them on as models to the human medical community.

For example, current research in dogs is testing a compound known as a metastasis blocking agent to see if it can inhibit the effect of matrix metalloproteinases, enzymes that eat the tissue between cells thus allowing the cells to break apart and scatter throughout the body. Cancerous cells can spread throughout the body because of these enzymes. If the metastasis blocking agent works, the spread of cancer can be stopped. The success of this research could significantly contribute to veterinary and human health.

"If this works, we could be looking at a significant advance in cancer therapy," says Dr. Kitchell.

Blocking the enzymes known to spread cancer is an example of cytostatic therapy. Traditional cancer treatment is cytotoxic, killing cancer cells but causing side effects in the patients. The use of cytostatic therapy could turn cancer from a chronic fatal disease to a chronic manageable disease, like diabetes mellitus.

The College is a leader in this project, with veterinary research trials ahead of human trials of a similar compound. The advantage of conducting trials first with animal patients is that enzymes such as matrix metalloproteinases also serve normal functions in the body, and the negative effects of blocking them are relatively unknown. And since cancer is the leading cause of death among dogs and cats, Dr. Kitchell and her team of researchers can study the naturally occurring disease in patients whose owners agree to the trial, rather than inducing the disease in healthy animals.

Vaccines, Genes, and More
On the immunotherapy front, Dr. Kitchell's team is examining anti-cancer vaccine strategies that would recruit the immune system to identify and kill cancer cells or clean up the cancer cells left after chemotherapy, radiation, and surgery.

In the research lab, the team is working on several molecular biology projects, one of which has involved cloning genes for matrix metalloproteinases from the dog. Cloning the genes makes the recombinant protein, which in turn allows one to create antibodies against the protein. This work could ultimately lead to early-detection diagnositic kits as well as improved treatment for specific cancers.

Another project involves studying the impact of compounds that might inhibit cancer cell immortalization. Normal body cells have a finite number of divisions in their lifetime. For example, after skin cells age and become senescent, the skin begins to wrinkle and heals more slowly. Cancer cells, on the other hand, can continue to divide well beyond the normal cell life expectancy, growing within the body and spreading the cancer. Dr. Kitchell's research team is evaluating compounds that could stop immortalization of cancer cells.

Anti-cancer drugs are also being studied. Dr. Kitchell is experimenting with time-released chemotherapy delivery systems that deliver drugs directly into a tumor. She is also examining markers of resistance to anti-cancer drugs so that she can predict which drugs will be best for patients.

Bone Transport Studies Benefit Children
Last spring, Dr. Nicole Ehrhart found that a new process called bone transport could spare the limbs of dogs with bone cancer. The technique of growing new bone with the help of a special ring fixture, known as an Ilizarov, was thought to hold potential benefit for humans--especially children--with bone cancer as well. Human bone had been regenerated in patients who had been the victims of accidents, but it was unclear how chemotherapy would affect the bone growth.

According to Dr. Ehrhart, continued study proves that chemotherapy can be given to patients without harming the new bone. Therefore, human cancer patients receiving chemotherapy are viable candidates for this new bone-sparing device.

Now this study of the effects of chemotherapy on bone growth has raised a new initiative for the veterinary oncology team. Though chemotherapy may not harm bone growth, radiation has been found to be an inhibitor. Dr. Ehrhart's latest challenge is to find out how to overcome the negative effects of radiation.

Radiation shuts down normal tissue processes while it stops the growth of a tumor. Dr. Ehrhart would like to discover how to "turn back on" the normal tissue growth. Currently she is studying bone morphogenic proteins--growth factors that encourage the growth of bone--to see whether they might be helpful in facilitating normal tissue processes.

Dr. Ehrhart is also working with pediatric oncology scientists from the University of Arkansas Medical School to discover how the signaling pathways of stem cells are changed. As Dr. Ehrhart explains, "Stem cells circulate throughout the body to help regenerate damaged tissue. During radiation treatments, stem cells are not killed, but they are not able to receive signals to enable them to turn into their respective tissue." Discovering how these signaling pathways are changed may lead to answers on why radiation inhibits bone growth.

Chemo and Surgery: A One-Two-Three Punch
In another instance of human and veterinary medicine working hand in hand, Dr. Kitchell and Dr. Ehrhart are investigating how chemotherapy treatment before bone surgery could give dogs a better chance at surviving bone cancer.

Human medicine studies have already shown that in patients with bone cancer, those who receive chemotherapy before surgery, as opposed to after surgery, could have a survival advantage. This evidence came to light quite accidentally, as doctors needed to treat the cancer of patients who had to postpone surgery until their prostheses could be custom-made.

"Traditionally with bone cancer, we've done surgery and then chemotherapy," says Dr. Ehrhart, who throughout the next year will be treating canine patients requiring surgery with chemotherapy both before and after their surgical procedure.

Nutrition Support for Patients
Dogs, though, are not the only focus of Ehrhart's studies. She knows that cats suffering from cancer lose a significant amount of weight during the course of their illness. She would like to find out what happens to body tissues, including fat, muscle, and bone, during cancer treatment. It is unclear whether the weight loss stems from loss of fat or muscle. It is also unclear whether the loss of tissue can be attributed to the cancer itself or to the diet of the cat.

The study will require 100 cats per year for at least two years. Owners will receive some compensation for allowing their cats to participate in the study.

According to Dr. Ehrhart, her goal is to see "what we can do to improve cats' quality of life as well as quantity of life. We want to give them optimal nutritional content."

Working Together for a Cure
These projects may vary in scope and size, affecting animals and humans, large and small, but the ultimate goal of finding a cure for cancer underlies each study.

"Cancer is one of the medical battlefields of modern life. The thought that motivates me the most is the knowledge that, one day, a child will not have to have an amputation because of our work," says Dr. Ehrhart. "The idea that we have contributed to human cancer research and yet hundreds of dogs and cats with cancer will also benefit, is evidence that physicians and veterinarians are truly practicing one medicine. We are all fighting the same battle."

From left: Drs. Gordon Baker, Barbara Kitchell, and Pamela Jones, of the College of Veterinary Medicine, accept a check for $50,000 from Dr. Michele Habrecht, Purina's technical support manager.

Ralston Purina Funds Veterinary Oncology Residency
Ralston Purina is contributing to new learning about how nutrition can help dogs and cats with cancer by funding a comparative oncology medicine residency at the University of Illinois College of Veterinary Medicine.

Purina recently renewed its commitment to continue funding the oncology residency by providing $50,000 during two years. Pam Jones, a 1998 graduate of Colorado State University College of Veterinary Medicine and Biomedical Sciences, will continue in her second year as the Purina comparative oncology medicine resident. Dr. Jones will study the effect of specific nutrients in helping animals maintain normal tissue while undergoing radiation therapy.

"The University of Illinois oncology residency allows Purina to be involved with research aimed at advancing the role of nutrition in the field of cancer medicine, says Dr. Aine McCarthy, Purina's director of veterinary professional communications. "It also helps to increase awareness of the importance of nutrition in veterinary care overall and presents an opportunity to share the science that goes into learning more about nutrition for oncology patients."

Funding for the oncology residency comes from the Purina College Program, which conducts educational outreach activities at all U.S. veterinary schools and veterinary residencies at Tufts, Minnesota, and UC-Davis as well as at Illinois. Ralston Purina, the world's largest producer of dry dog and dry and soft-moist cat foods, also produces a veterinary dietary line for dogs and cats with special nutritional needs.