01657: Defining New Therapeutic Approaches for Osteosarcoma through Genome Wide Screening and Comparative Oncology
Grant Status: Open
Grant Amount: $31,500
Dr. Carl Walkley, PhD, St Vincent's Institute of Medical Research
January 1, 2012 - December 31, 2012
Sponsor(s): Afghan Hound Club of America, Flat-Coated Retriever Foundation, Great Pyrenees Club of America
Abstract Bone cancer, or osteosarcoma, is a common and life-threatening problem for primarily large breed dogs. While surgical techniques and use of chemotherapy have improved the length of time dogs remain free of disease following surgical removal of the tumor, the vast majority of dogs develop drug-resistant tumor spread, or metastasis. Indeed, in some dogs, the tumor has already spread at the time of diagnosis, resulting in only palliative treatment options. There is a need to develop new drugs to improve the survival for canine osteosarcoma. The unraveling of the genetic code in multiple species, including humans, mice and dogs, has lead to an ever-increasing understanding of the genetic basis of cancer, including osteosarcoma. In addition, the use of new technologies to silence individual gene function allows us to assess the contribution of large numbers of genes to osteosarcoma cell survival. This project utilizes the high-throughput screening technology (siRNA libraries) in human and dog osteosarcoma cells. Tumor cells are incubated with siRNA in combination with doxorubicin, one of the most effective chemotherapy drugs used to treat canine osteosarcoma. Genetic targets that, when knocked down by siRNA, improve the response to doxorubicin, will be selected for further validation in multiple samples of canine and human osteosarcoma. Those targets that appear most promising in both species will be further evaluated as new drugs to combine with doxorubicin in a clinical trial for dogs with osteosarcoma.