Research of Treatments for Mast Cell Tumor May Help Boxers

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Growing up in a family with a pet Boxer, Joyce Baker Brown fell in love with the breed. Her entire life she has had Boxers and counts herself lucky that her dogs have had few of the health concerns common in the breed. Except for one: Four have died of mast cell tumors (MCT).

For unknown reasons, Boxers have an increased risk for MCT, though any breed of dog or mixed breed can develop the cancer. The prognosis for an individual dog with MCT depends on factors such as tumor grade, tumor stage and whether surgery is possible to completely remove the tumor. 

The most common skin cancer in dogs, mast cell tumor is a cancer of a type of white blood cell found throughout the body. Mast cells are an important part of the immune system. When these cells replicate out of control, they form an aggressive cancer. 

Kit Inhibiting Drugs & Checkpoint Inhibitors 

Investigations into innovative treatments for MCT include two studies funded by the AKC Canine Health Foundation. A personalized medicine approach to MCTs that are more aggressive because they have a mutation in the c-kit gene looked at whether treatment with KIT inhibitors yielded treatment success. A study of checkpoint molecules, also supported by the American Boxer Charitable Foundation, is progressing this novel cancer immunotherapy in dogs. 

Douglas Thamm, VMD, DACVIM (Oncology), the Barbara Cox Anthony Professor of Oncology, 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,” says Dr. Thamm. “As the proportion of dogs with c-kit mutations was not different between treatment groups, c-kit mutation status did not predict treatment response as we had hoped. 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. “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. There’s hope in the near future for completely changing the canine cancer treatment landscape, and that’s happening pretty quickly.” 

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