New Treatments for Mast Cell Tumor & DNA Testing for JLPP Offer Hope

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Advancements in treating canine diseases, such as cancer, come from innovative studies sometimes patterned after progress in human medicine. In this issue of the Dog Update, new therapies focused on checkpoint molecules and personalized medicine for mast cell tumor (MCT), the most common skin cancer in dogs, are featured. 

Meanwhile, genetic studies of the neurological disease juvenile-onset laryngeal paralysis and polyneuropathy (JLPP) in Rottweilers and Black Russian Terriers show how the gene mutation occurred in an ancestral founder long before either breed was formed. The fatal condition affecting puppies can be eliminated in both breeds, thanks to a DNA test.

Canine Mast Cell Tumor 
In the MCT personalized medicine research, Douglas Thamm, VMD, DACVIM (Oncology), the Barbara Cox Anthony Professor of Oncology at Colorado State University, led a multi-center study exploring the potential sensitivity of mast cell tumors with c-kit gene mutations to KIT-inhibiting drugs. A protein found on the surface of many different types of cells, the KIT protein also may be found in higher than normal amounts or in a changed form on some types of cancer cells, including MCT. The study was published in 2018 in the Journal of Veterinary Internal Medicine.

In the clinical trial, Dr. Thamm and his team compared the effectiveness of toceranib (TOC), a KIT inhibitor sold as Palladia™, and vinblastine (VBL), a chemotherapy drug, in treating dogs with MCT with and without c-kit gene mutations. “Our hypothesis was that MCT with c-kit mutations would have a superior response to toceranib compared to vinblastine,” Dr. Thamm says. 

“Neither the progression free survival time (length of time during and after treatment that a patient lives without getting worse) nor overall survival time (length of time from the start of treatment that a patient is still alive) was significantly different between the treatment groups,” Dr. Thamm says. “Further studies are needed, but this work has helped us to understand the value of these targeted drug therapies.”

Another Colorado State University researcher, Steven Dow, DVM, PhD, DACVIM, professor of immunology and director of the Center for Immune and Regenerative Medicine Clinical Sciences, is soon to complete a study of the effectiveness of OX40 checkpoint molecules as a targeted antibody for canine cancer immunotherapy. 

“Checkpoint molecules play a key role in regulating T-cell immunity against cancer,” Dr. Dow explains. “We are developing a second-generation immunotherapy for dogs that follows the first-generation PD-1 antibodies already underway. In this project, the team is characterizing canine OX40 antibodies to determine how they activate effector T cells in dogs. We want to see if they trigger an immune activation in tumor tissues." 

JLPP Ancestral Founders
A progressive, fatal neurological condition, JLPP is heartbreaking for those whose dogs inherit the disease. The condition was first recognized in Rottweiler puppies in the 1990s. Nearly 20 years later, an autosomal recessive gene mutation was discovered for a similar juvenile-onset disease in Black Russian Terriers. “Once we had the mutation in Black Russian Terriers, we were able to test Rottweilers to see if it was the same mutation,” says Dennis O’Brien, DVM, PhD, the Chancellor’s Chair in Comparative Neurology at the University of Missouri College of Veterinary Medicine. “It proved to be the same mutation.”

“It is likely the same founder mutation event was the source of the RAB3GAP1 gene mutation in both breeds,” Dr. O'Brien says. “Since a heavy-coated Russian breed was crossed with Standard Schnauzers and Rottweilers to produce the Black Russian Terrier, the mutation was probably in Rottweilers, then got passed on to Black Russian Terriers.”
 

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