Bone cancer affects many of the large breeds including the Doberman Pinscher, Golden Retriever, Great Dane, Greyhound, Labrador, Leonburger, and Rottweiler. In humans advanced stage breast cancer and prostate cancer metastasize to bone cancer. Finding a cure is a win-win for both humans and our canine companions.
Several of the other studies we have supported include:
Niche Conditioning for Metastasis in Canine Osteosarcoma (Dr. Hiro Tomiyasu, University of Minnesota). The goal of this project is to determine how bone tumors communicate with tissues at distant sites in order create favorable conditions for tumor cells to colonize and survive, thereby giving rise to metastasis. Recent work suggests that the tumors send out “scout parties” in the form of small cell fragments called exosomes. These exosomes deliver biologically active molecules that make distant sites welcoming for wayward tumor cells. This project is designed to find markers in the exosomes that will allow us to predict where and when the disease will spread, as well as to identify targets we can use to delay or prevent this spread.
We have found that the process of loading osteosarcoma exosomes is “active”. In other words, in each tumor there is a selection process that determines molecules that are loaded into or excluded from the exosomes. This results in unique packages, which are associated with the potential of the cells to disseminate to the lungs or other sites. We also have shown that exosomes modify the behavior of normal cells in lab cultures. This suggests that exosomes are also likely to modify the behavior of cells in the body, allowing metastasis to occur.
A next critical step in this project is to identify specific candidate molecules that prevent or favor metastasis.
Osteosarcoma Vaccine Study (Dr. Nicola Mason, University of Pennsylvania). The goal is to stimulate the dog's immune system to target OS cells that have survived chemo therapy by injecting a vaccine composed of a genetically modified Listeria bacteria. Listeria expresses a tumor marker known as Her2/neu. They are testing to determine if the bacteria will stimulate the patient's immune system to kill the bacteria and also kill cells that express Her2/neu, which is shown on 40% of OS tumors in canines and humans.
Genomics: Germline and Somatic Genetic Determinants of Osteosarcome Outcome (David Largaespade with Logan Spector, Subbaya Subramanian, and Dr. Jaime Modiano, University of Minnesota). This study compares genetic and epigenetic alterations in the germline and in somatic cells of humans, dogs and mice with osteosarcoma to identify events that are responsible for the spectrum of clinical behaviors observed in OS. Their goal is to discover genetic markers that predict risk for OS to make early screening and targeted therapies feasible. They believe the interspecies approach affords a broader view to understanding OS. GREYlong also contributed to this study.
Immunotherapy for Osteosarcoma (OSAL) (Dr. Vicki Wilke and Emily Lipsitz, University of Minnesota) . This study which will evaluate the safety and efficacy of non-pathogenic Salmonella organisms carrying an immune cytokine (IL-2) to mount specific anti-tumor responses in dogs with spontaneous osteosarcoma. This trial has current support from the Children's Cancer Research Fund and the Animal Cancer Care and Research Program of the University of Minnesota.
Osteosarcoma (OSA) Genetic Study (Dr. Guillermo Couto, Ohio State University). OSA is the most common cause of death in retired racing Greyhounds, yet it is very uncommon in AKC Greyhounds. This provides a unique opportunity to evaluate genes involved in the development and progression of OSA in the breed. In collaboration with Dr. Alvarez's lab in Nationwide Children's Hospital we are currently evaluating samples from retired racers and AKC dogs with and without OSA, in order to identify genes involved in the development of this deadly disease. In addition, because racing Greyhounds are tattooed and their pedigrees easily obtained on line, we are evaluating pedigrees in dogs with and without OSA for statistical comparison. In addition, in collaboration with Dr. Breen's (NCSU) and Lindbladh-Toh's (The Broad Institute) labs we are evaluating OSA genes in Greyhounds and other breeds, and evaluating their role in response to treatment and prognosis. Finally, we are evaluating novel treatment protocols for both Greyhounds and dogs of other breeds with OSA.
Evaluation of Cyclopamine as a Therapy for Bone Cancer (Dr. Heather Wilson, Texas A&M). Cancer arises from a single mutated cell possessing the power to replicate and form a tumor. There are many theories as to the cause and progression of this process. One theory states that a cell with stem cell capabilities divides to produce new tumor-initiating cells and daughter cells. Identifying pathways that can increase sensitivity to therapeutic intervention is paramount to finding a cure for bone cancer. Cyclopamine, a chemical found in the corn lily plant, inhibits the pathway responsible for normal embryo development and directing the regeneration of tissues. This study will research Cyclopamine's effectiveness at inhibiting tumor-initiating cells in canine osteosarcoma cell lines. The goal is to provide a new targeted therapy for pets with osteosarcoma. The final report issued stated that the research team discovered that at high does cyclopamine inhibits an important signaling stem-cell pathway used by tumor-initiating cells. Based on these findings, researchers believe that adding cyclopamine during and after traditional chemotherapy may help inhibit the growth and spread of bone cancer in dogs. They plan to purse further research in this regard.
Examining Drug Targets for Treating Bone Cancer (Dr. Joseph J. Wakshlag, Cornell University). Preliminary evidence in humans suggests that blocking a traditional pathway of inflammation, know as the lipoxygenase (LOX) pathway, can inhibit the growth of certain cancer cells. This study examines the role the LOX pathway plays in canine osteosarcoma development and whether inhibiting it can kill bone cancer cells. The findings may lead to a new drug therapy for osteosarcoma.
MicroRNA Expression Profiling of Canine Osteosarcoma (Dr. W.C. Kisseberth, Ohio State University). Using the assumption that cancer is fundamentally a genetic disease, by studying the MicroRNA expressions, investigators hope to identify new molecular targets for therapy, which will lead to better treatment of this disease.