GPCA Funded Grants

Osteosarcoma (OSA), or bone cancer, affects 8000-10,000 dogs in the USA annually. Large and giant breeds are at a much higher risk for this disease, suggesting that inherited risk factors are involved. Roughly 10-15 percent of Rottweilers and 15-20 percent of Greyhounds get the disease. The principal investigators of this study have identified several regions of the canine genome that are assoiciated with an increased risk for OSA in Rottweilers. A similar study is underway for Greyhounds and is expected to identify additional regions of importance. The purpose of this study is to identify actual genes and mutations causing the increased risk for bone cancer in Rottweilers and Greyhounds. The researchers intend to then determine the frequency of mutations in these genes in OSA in other breeds as well as in tumors. This work should allow the development of specific genetic tests for carriers of OSA and suggest further studies leading to improved treatments for bone cancer.

GPCA Health Committee Commentary:

This study is a continuation of a study previously funded and supported by the GPCA, "Hereditary Mutations in Genes Assoiciated with Osteosarcoma in Large Breed Dogs". This is a 2 year study and willaextend the information gathered to include other breeds. The initial study identified 7 loci on the genetic code for Rottweilers and Greyhounds which appear only in dogs affected with OSA. The intent is to further refine the information on those 2 breeds and to investigate the 7 loci in additional breeds of which Great Pyrenees is included.

Samples from Great Pyrenees affected with osteosarcoma are requested by the researcher. Also, we need to submit samples from older unaffected dogs (defined as 8yrs or older with no signs of OSA) to use as controls. See the section below regarding submission of samples to The Broad Institute or go directly their site: dog-info@broad.mit.edu

Update, May 09: Interim report from this study indicates that they have received samples from 22 affected Pyrs, 56 controls and 25 older healthy controls. For the fine mapping they have matched 17 affected with 17 controls for Pyrs. There is initial confirmation that some of the loci associated with Rottweillers and OSA are also present in Pyrs with the disease. In addition to osteosarcoma they are also looking to see if the loci is present in other cancers ( hemangiosarcoma, mast cell, melanoma and others).

Active Grant No: #976 Investigating the Role of STAT3 Activation in Canine Osteosarcoma

Osteosarcoma (OSA) is the most common bone tumor in dogs and despite aggressive treatment with amputation and chemotherapy, nearly all dogs die of their disease within 2 years of diagnosis. Unfortunately there have been no significant advancements in the treatment of OSA over the past 15 years. The laboratory at Ohio State University under the direction of Dr. London has been working on defining the molecular biology of OSA and has recently identified a cellular pathway that appears to be important for OSA cell survival. This involves a protein called STAT3 that is often abnormally activated in human cancers and has not yet been ivestigated in canine cancers. Several canine OSA cell lines tested were found to have excessive STAT3 activation indicating that this pathway may be useful for therapeutic intervention. In support of this, Dr. London's preliminary data demonstrates that an inhibitor of STAT3 activation is capable of killing canine OSA cell lines. The purpose of this grant is to perform a more thorough evaluation in canine OSA and by testing the ability of new STAT3 inhibitors developed at Columbus Children's Hospital to kill OSA cell lines. These studies will define the role of STAT3 in canine OSA and lay the groundwork for future clinical trials of STAT3 inhibitors in dogs with devastating disease.

GPCA Health Committee Commentary:

While we are hoping this study results in an effective treatment for canine osteosarcoma, currently no samples from Great Pyrenees are being requested. This molecular pathway once developed should not be breed specific.

Studies/Research closed or completed which have received funding from the GPCA preivously:

Mapping Genes Associated with Osteosarcoma in Large Dog Breeds #373A Research headed by Dr. Kerstin Linblad-Toh, The Broad Institute Downloadable Report

Inhibition of Collagenolysis in Canine Cruiciate Ligament During Rupture #2405 Research headed by Peter Muir, BVSc, PhD, University of Wisconsin Downloadable Report

For more information in participating - contact Flo Laicher @ pyrshire@comcast.net

Cancer(s) Affecting The Great Pyrenees

See above per specific current studies. As we receive updates on previous research we will post here.