Making Advanced Discoveries in Golden Cancers

The three-year project will examine genetic traits that contribute to risk and progression of hemangiosarcoma and lymphoma.

Golden Retrievers have been one of the most popular breeds in America for decades, but unfortunately these dogs also have one of the highest incidences of cancer. Hemangiosarcoma and lymphoma account for more than 30 percent of the deaths in this breed. Although breed susceptibility to cancer was first reported 30 years ago, the relationship between inherited traits and susceptibility for these cancers is still not known. The Golden Retriever Foundation and Morris Animal Foundation are funding this study to discover and characterize heritable and somatic cancer mutations in Golden Retrievers.

The three-year project will examine genetic traits that contribute to risk and progression of hemangiosarcoma and lymphoma in Golden Retrievers. The long-term goal is to understand what causes these diseases. Because both cancers occur with such high frequency, reducing their incidence (while retaining the positive phenotypes of the breed) will be a complex task, but the development of reliable genetic tests would allow breeders to build programs whereby high-risk combinations of factors could be avoided. In addition, effective strategies could be developed to control and treat hemangiosarcoma and lymphoma in Golden Retrievers and other dogs. What is learned from this research may also lead to effective prevention and treatment strategies for these diseases in people and other breeds.

Co-sponsored with the Morris Animal Foundation, Grant Number: D10CA-501

RESEARCHERS

Jaime F. Modiano, VMD, PhD
University of Minnesota

Matthew Breen, PhD, CBiol, FSB
North Carolina State University

Kerstin Lindblad-Toh, PhD,
Uppsala University, Sweden

Comment: Because of Dr. Modiano’s work with PWDs in the past, this will definitely benefit our breed.

Enrichment for Canine Cancer Stem Cells by In Vitro Manipulation and Chemotherapy

This study will look at cancer stem cells to develop therapeutic strategies that target these cells and generate new, more effective treatment approaches with fewer side effects for dogs with cancer.

Cancer therapy for dogs has become more common, but treatment doesn’t always lead to long-term remission, and some therapies have debilitating side effects. A major reason for failure of conventional treatments may be their inability to eradicate cancer stem cells. These cells are self-renewing, can spread to new areas of the body and can give rise to daughter cells, which can rapidly divide. This means that even one cancer stem cell left behind after treatment can cause the cancer to return. Cancer stem cells appear to be less susceptible to traditional cancer therapies, such as chemotherapy.

Researchers will study cancer stem cells to help them develop therapeutic strategies that target these cells and generate new, more effective treatment approaches with fewer side effects for dogs with cancer. Aric M. Frantz works jointly with Dr. Modiano

Co-sponsored with the Morris Animal Foundation, Grant Number: D09CA-405

RESEARCHERS

Aric M. Frantz, CVM, ACCR
University of Minnesota

Studying How Mast Cell Tumors Become Malignant

Researchers will analyze expression of miRNAs associated with aggressive mast cell disease and begin to define how they may promote aggressive progression of tumors in dogs.

Mast cell tumors are the most common skin tumor in dogs, and they are often fatal. Unfortunately, identifying the tumors likely to become malignant is challenging because little is known about how mast cells transform from benign to malignant. MicroRNAs (miRNAs) are small non–protein-coding RNAs involved in the initiation and progression of cancer in humans. Researchers will analyze expression of miRNAs associated with aggressive mast cell disease and begin to define how they may promote aggressive progression of tumors in dogs. This will help veterinarians better determine the prognosis for dogs with these tumors and more effectively treat them.

Co-sponsored with the Morris Animal Foundation, Grant Number: D09CA-060

RESEARCHERS

Cheryl A. London
DVM, PhD Dipl. ACVIM (Oncology)
Ohio State University

Determining Risk Factors for Lymphoma

To determine whether dogs with genetic defects in an important detoxification enzyme, called GSTT, are more likely to develop lymphoma.

Lymphoma, one of the most common cancers in dogs, is fatal in most patients. Though the underlying causes of the disease aren’t understood, exposure to industrial pollutants and commonly used herbicides may increase a dog’s risk of lymphoma. Research shows that humans exposed to environmental chemicals have a higher risk for developing lymphoma, and genetic defects in the enzymes that remove environmental chemicals from the body increase this risk.

This study will determine whether dogs with genetic defects in an important detoxification enzyme, called GSTT, are more likely to develop lymphoma. The results will provide insight into the genetic and environmental risk factors for lymphoma in dogs.

Co-sponsored with the Morris Animal Foundation, Grant Number: D09CA-029

RESEARCHERS

Lauren A. Trepanier, DVM, PhD
University of Wisconsin

Evaluating Drugs to Treat Hemangiosarcoma

Tyrosine kinase inhibitors may have the potential to control the growth of hemangiosarcoma.

Hemangiosarcoma remains one of the deadliest canine cancers. Despite treatments such as chemotherapy, immunotherapy and surgery, dogs rarely live beyond six months after diagnosis. New approaches are needed to improve the survival time of dogs afflicted with this devastating disease.

This study will expand on the team’s previous research into a novel class of drugs – tyrosine kinase inhibitors – that may have the potential to control the growth of hemangiosarcoma. The results will help to clarify abnormalities that contribute to hemangiosarcoma proliferation and may ultimately lead to new treatment options for this aggressive cancer.

Co-sponsored with the Morris Animal Foundation, Grant Number: D08CA-050

RESEARCHERS

Stuart C. Helfand, DVM
Oregon State University

Investigating a Noninvasive, At-Home Diagnostic Technique for Gastrointestinal Disorders

Gastrointestinal disorders are common in dogs and are often associated with a change in the rate food moves through the stomach and intestines. This study uses a noninvasive, wireless sensor capsule to determine the gastrointestinal transit in dogs. The information will help veterinarians to better diagnose gastrointestinal diseases, including bloat, gastritis and inflammatory bowel disease, while dogs are in their home environment.

Co-sponsored with the Morris Animal Foundation, Grant Number: D10CA-106

RESEARCHERS

Pedro L. Boscan, DVM, Phd
Colorado State University

Genetic Analysis of Hypoandrenocorticism in Nova Scotia Duck Tolling Retrievers

Addison’s disease, also known as hypoadrenocorticism, is a deficiency of hormones that are produced by the adrenal glands and help regulate a dog’s metabolism, blood pressure, electrolyte balance and stress response. Though the disease is relatively uncommon in dogs, certain breeds—including Nova Scotia Duck Tolling Retrievers, Bearded Collies, Great Danes, Leonbergers, Portuguese Water Dogs, Standard Poodles and West Highland White Terriers—have a much higher risk than the general dog population.

Results

Researchers identified a region of the genome that is associated with the development of Addison’s disease in Nova Scotia duck tolling retrievers. Additionally, it appears that dogs that are homozygous (both chromosomes carrying the same genes) with respect to this region are at greater risk of developing Addison’s disease, even at a young age (under 2 years). Although additional genes are likely involved, this information is the first step toward understanding the genetics of this disease and developing a genetic test that will help eliminate Addison’s disease through informed breeding practices. This fellowship training grant also provided hands-on training for a veterinarian who is pursuing a research career.

Co-sponsored with the Morris Animal Foundation, Grant Number: D08CA-402

RESEARCHERS

Angela M. Hughes, DVM
University of California at Davis

Pharmakokinetics and Pharmacodynamics of Hydroxyzine in Healthy Dogs

Atopic dermatitis is a common allergic skin disease in dogs and humans. Antihistamines are among the most commonly prescribed treatments. Unfortunately, the optimal dosages of commonly used antihistamines have never been scientifically determined, and their effects have not been validated in dogs.

Researchers at North Carolina State University wanted to determine whether hydroxyzine, one of the drugs most commonly used to treat atopic dermatitis in dogs, truly provides an antihistamine effect and, if so, what the appropriate dose is for dogs.

Results

The researchers successfully determined that hydroxyzine does produce an antihistamine effect and confirmed that a twice-daily dose is appropriate, versus the previously standard prescription of three times a day. They also discovered that when hydroxyzine is administered orally or intravenously the drug breaks down into its simpler form (cetirizine), and this simpler form is responsible for the actual antihistamine effect. They now want to look at this drug as a more effective treatment for atopic dermatitis.

Co-sponsored with the Morris Animal Foundation, Grant Number: D07CA-029

RESEARCHERS

Thierry Olivry, DrVet, PhD, Dip. ECVD, Dip. ACVD
North Carolina State University

Pooled Association Mapping for Canine Hereditary Disorders

To develop a system that will map genetic traits causing health problems.

More than 450 canine genetic traits are listed on the Online Mendelian Inheritance in Animals list. These traits affect all body systems in dogs and can cause health problems ranging from mild disease susceptibility to severe illness and death. Researchers will use a genetic tool called the Affymetrix Canine SNP Chip to develop a mapping strategy using pooled DMA samples that will map genes for hereditary canine disorders. This method promises to be 10 times more efficient and cost effective than current methods for analyzing canine inherited traits. Once this method is validated, it will be used to map a series of hereditary retinal disorders affecting multiple breeds.

Co-sponsored with the Morris Animal Foundation, Grant Number: D07CA-085

RESEARCHERS

Gregory M. Acland, BVSc
Cornell University

Dr. Acland is a professor of medical genetics at Cornell University and an adjunct p of ophthalmology at the University of Pennsylvania. He received his veterinary degree from the University and completed a residency and postdoctoral work at the University of Pennsylvania.