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0002646: Characterization of Receptor Tyrosine Kinase Dysfunction in Malignant Histiocytosis

Grant Status: Closed

Grant Amount: $28,397.25
Dr. Cheryl A. London, DVM PhD, University of California, Davis
October 1, 2003 - September 30, 2005
Sponsor(s): American Boxer Charitable Foundation, Berner Lovers, Bernese Mountain Dog Club of America, Flat-Coated Retriever Foundation, Golden Retriever Foundation
Breed(s): Bernese Mountain Dog, Boxer, Flat-Coated Retriever, Golden Retriever, Rottweiler
Disease(s): Histiocytosis

Abstract

Malignant histiocytosis (MH), while rare in people, occurs frequently in certain breeds of dogs including Rottweilers, Golden Retrievers, Flat-Coated Retrievers and Bernese Mountain Dogs. There is no effective therapy for this disease and nearly all patients die within two to four months of diagnosis. The prupose of this proposal is to evaluate MH tumor specimens for mutations in genes that may contribute to the development of this devastating cancer. The genes of interest are those that code for proteins known as growth factor receptors. These proteins are present on the surface of the cell and when stimulated by growth factors, signal into the cell promoting cell survival and growth. Dysregulation of growth factor receptors is a common mechanism through which normal cells undergo transformation into cancer cells. Significant research has been directed toward the development of inhibitors capable of blocking the function of dysregulated receptors. Recent success of this approach has been realized with the inhibitor Gleevec in the treatment of chronic myelogenous leukemia in people. The purpose of this proposal is to identify growth factor receptors that are dysregulated in MH to provide the foundation for future clinical application of growth factor receptor inhibitors in the treatment of MH.
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