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Technology Transfer Boosts Oncology

How methodologies from the veterinary world are being adopted by human medicine.

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The trickle-down theory has become a mainstay in veterinary medicine.

Techniques, instruments and equipment from human medicine are regularly adopted for use with animals, improving outcomes for thousands of patients.

But now some new oncological methodologies in the veterinary world promise to return the favor.

At the University of California, Davis, School of Veterinary Medicine, a team of 19 veterinary oncologists and other scientists have formed a partnership with researchers from more than a dozen scientific disciplines to investigate new cancer therapies for both animals and humans.

In an article published in the 2004 Spring/Summer issue of Synthesis, a publication of the UC Davis Cancer Center, Cheryl London, DVM, Ph.D., Dipl. ACVIM, assistant professor of surgical and radiological sciences, said that the benefits of the center's research can flow both ways, aiding humans and animals alike.

One clinical study used the multi-targeted kinase inhibitor SU11654 to slow the growth of, or even cure, certain types of tumors. Fifty-seven dogs were studied in the trial, each with advanced end-stage cancers. Of those, the disease was completely halted in 16 cases and 11 experienced shrinkage of the tumor. In six cases, complete remission was achieved.

In the article, Dr. London said that the testing process for new drugs can be expedited in animals since veterinarians aren't subject to the stringent regulation imposed on human physicians. In addition, costs are generally lower to treat the animal population, resulting in less expensive research.

London is now testing a drug known as 2-ME2, which promises to attack sarcoma cells in dogs and cats. If successful, the trial could lead to improved therapies for human cases of prostate cancer, metastatic breast cancer and multiple myeloma.

Vaccines for Cancer

At the Animal Medical Center in New York City, Phillip J. Bergman, DVM, MS, Ph.D., Dipl. ACVIM, is conducting a study using a human DNA melanoma vaccine to treat canine tumors.

Dr. Bergman, who heads the Donaldson-Atwood Cancer Clinic at AMC, said malignant melanomas usually spread quickly and fail to respond to standard therapies.

The usual treatment is surgical removal of the tumor in conjunction with chemotherapy, radiation or immunotherapy, but survival rates are low because of the high incidence of recurrence.

The DNA vaccine underwent pre-clinical testing at Memorial Sloan-Kettering Cancer Center and is now being used to inoculate dogs against the disease.

Results have been encouraging: The trial's fourth study revealed a dramatic increase in patient survival rates, with a median survival time of 389 days.

When dogs with advanced  malignant melanoma are treated with standard therapies alone, the median survival is 60 to 90 days.

The study found no toxicity in any of the vaccinated dogs.

With the vaccine's success in fighting malignant melanoma, Bergman is evaluating its use in other types of canine cancers including lymphomas.

His team plans to apply for commercial approval of the vaccine in the coming months. He also hopes it may have applications in treating human melanoma.

Fighting With Lasers…

Michael Lucroy, DVM, MS, Dipl. ACVIM, is investigating the use of photodynamic therapy using lasers at Purdue University's School of Veterinary Medicine. The technique uses red laser light to activate anti-cancer drugs that selectively attack tumors.

"The light by itself doesn't damage the tissue, and neither does the drug by itself. You have to have the drug plus the light to have an effect," Dr. Lucroy said.

The program has had success with skin cancer and some oral cancers, Lucroy said, because those types are the most accessible.

"We've also had reasonably good luck with intranasal tumors, and some early success with urinary bladder cancer," he said. For the latter, Lucroy uses a cylindrical diffuser with optical fibers to irradiate the more deep-seated tumors.

Because the drugs are activated only by red light, a standard surgical laser with its infrared beam won't work for PDT, Lucroy said.

And because the specialized laser used in the procedure costs up to $100,000, it will probably be some time before the technique filters down to local clinics, he said.

But Lucroy added that "at some point, at least for skin cancer and those that are more easily accessible, it will find its way into a general practice setting."

…And With Microwaves

At the North Carolina College of Veterinary Medicine, a similar technique is being developed using microwaves instead of lasers.

The project, a joint venture with Duke University, involves the injection of drug-infused liposomes into the bloodstream, said Marlene Hauck, DVM, Ph.D., Dipl. ACVIM, assistant professor.

The liposomes accumulate in the tumor, which is then heated with microwaves, prompting the liposome to release its chemotherapy agent.

"The engineers at Duke built microwave applicators that are specifically designed to heat tumors," said Dr. Hauck, who reported the recent completion of a Phase I trial with heat-sensitive liposomes that went directly into human trials.

"Many times drugs are tested in companion animals as a way of quickly determining toxicity levels, how the drugs are handled by patients and whether they're going to have any efficacy," Hauck said.

"That can sometimes happen much more rapidly in the veterinary world than in human oncology."

The college is also conducting a study of vaccine-associated sarcomas in cats, which are difficult to treat surgically because of metastasis or recurrence in approximately half of all cases.

Therapy involves implanting the DNA code for interleukin-12 (IL-12) into a tumor in order to activate an immune system response. The expression of the gene is controlled by heating the site.

"In essence, we're turning the gene on so it can produce its product, which in this case is an immunotherapy cytokine in the tumor," Hauck said.

"Ultimately we hope it will stimulate the patient to develop an immune response against the cancer.

"The trial is a proof of principle feasibility study where we demonstrate that we can get thousandfold higher levels in the tumor versus what we see in the plasma with this particular cytokine."

Precision Radiation

Gregory K. Ogilvie, DVM, Dipl. ACVIM, is using intensity modulated radiation therapy to more precisely target tumors at California Veterinary Specialists' Angel Care Cancer Centers, in San Marcos and Murrieta, Calif.

Instead of a large beam of radiation passing through the body, IMRT uses thousands of small beams that target the tumor from many angles.

"This sculpted radiation therapy provides highly directed, precise radiation to places such as the brain and spinal cord with extreme precision while limiting adverse effects," said Dr. Ogilvie, the center's director.

The Angel Care Cancer Center also uses docosahexaenoic acid treatments to enhance the effects of radiation and chemotherapy, and as an adjuvant therapy to prevent cancer progression and metastasis.

Numerous studies have shown that fatty acids such as DHA can delay or prevent the formation and spread of tumors, Ogilvie said.

Prevention by Delay

"The use of fatty acids, such as docosahexaenoic acid, at the CVS Angel Care Cancer Center is designed to enhance disease-free interval, survival and quality of life after surgery by reducing the rate of cancer development or incidence," Ogilvie said.

"This concept, known as 'cancer prevention by delay,' has recently been recognized and is an important mechanism behind several therapeutic agents. We are finally evolving to a higher level of care where quality of life is everything."

These new developments in veterinary oncology continue to improve survival rates and quality of life among animals, and many of the same techniques are quickly being adopted in human medicine.

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