267: Investigation into Combined Molecular Approaches to Treat Hemangiosarcoma

Grant Status: Closed

Grant Amount: $105,840
Dr. David J. Argyle, PhD, University of Wisconsin, Madison
July 1, 2004 - June 30, 2005
Sponsor(s): American Boxer Charitable Foundation, Collie Health Foundation, Flat-Coated Retriever Foundation, Golden Retriever Foundation, Irish Wolfhound Club of America, Inc., Scottish Terrier Club of America, Starlight Fund
Breed(s): -All Dogs
Research Program Area: Treatment

Abstract

Hemangiosarcoms (HSA) is a common and fatal cancer in dogs for which there is no effective treatment. Despite surgery and intensive chemotherapy, the median survival time for dogs diagnosed with HSA is little more than six months. From our own studies on canine cancer, expression of the enzyme telomerase allows cancer cells to become immortal and has emerged as a central and near universal marker of cancer, making it a candidate target for novel therapies. In this study we will explore the value of telomerase inhibition to treat HSA using the novel mechanism of RNA interference (RNAi). Our hypothesis is that potent inhibition using this technique will inhibit the immortal phenotype of the cancer cells and cause them to die. However, it is possible that a combined approach, targeting two molecular pathways, may offer greater therapeutic benefit. Consequently, we will also explore the potential synergism of combining telomerase inhibition with an alternative inhibitor of a further mechanism involved in cancer (receptor tyrosine kinase inhibition) on targeting this highly malignant tumor. In this we will use in vitro cell culture techniqus for initial inhibition studies followed by studies in a novel canine HSA model system to ascertain the potential clinical merit of this approach for dogs with HSA.

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