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1759: Disrupting the Differentiation of Cancer Stem Cells to Prevent the Spread of Hemangiosarcoma

Grant Status: Open

Grant Amount: $233,914

Dr. Jaime F Modiano, VMD PhD, University of Minnesota

January 1, 2013 - December 31, 2015

Sponsor(s): American Belgian Tervuren Club, Inc., American Spaniel Club Foundation, Australian Shepherd Health & Genetics Institute, Australian Terrier Club of America, Briard Club of America Health & Education Trust, Dachshund Club of America, Inc., Flat-Coated Retriever Foundation, Golden Retriever Foundation, Great Dane Club of America, Ibizan Hound Club of the United States, Irish Setter Club of America Foundation, Italian Greyhound Club of America, Keeshond Club of America, Keeshond Donors Circle Trust, Leonberger Health Foundation, Norwegian Lundehund Association of America, Inc., Old English Sheepdog Club of America, Poodle Club of America Foundation, Portuguese Water Dog Foundation, Rottweiler Health Foundation, Saluki Health Research, Inc., Skye Terrier Club of America, Starlight Fund, TarTan Gordon Setter Club, University of Minnesota - DAF for EIC Royalties, Versatility in Poodles, Inc., Welsh Springer Spaniel Club of America, White Shepherd Genetics Project

Breed(s): Airedale Terrier, Australian Shepherd, Belgian Sheepdog, Bernese Mountain Dog, Bouvier des Flandres, Boxer, Flat-Coated Retriever, German Shepherd Dog, German Shorthaired Pointer, Keeshond, Labrador Retriever, Portuguese Water Dog, Saluki, Siberian Husky

Disease(s): Hemangiosarcoma

Research Program Area: Oncology - Hemangiosarcoma

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Abstract

Hemangiosarcoma is a rapidly fatal disease. The lifetime risk is alarmingly high for some breeds like Golden Retrievers (~20% will die of this disease) and Portuguese Water Dogs (~15% will die of this disease). The risk of hemangiosarcoma is not limited to just these breeds but is considered a research priority for 40 different breed Parent Clubs. Despite considerable efforts to find effective treatments, the outcome for dogs with hemangiosarcoma has changed very little over the past 30 years. Recent evidence suggests hemangiosarcoma conforms to the "cancer stem cell" model, where a defined subset of cells is responsible for initiating and maintaining the tumor. These cells are resistant to conventional therapies and are very adaptable, being able to survive in a variety of tissues in the body. For this project, Dr. Modiano proposes to reduce the malignant potential of hemangiosarcoma stem cells by forcing them to terminally differentiate into cells which can no longer self-renew. He further proposes that by disrupting their ability to self-renew he will enhance the sensitivity of these cells to conventional and targeted therapies and improve the outcomes of dogs with this disease.