Funded Research
August 15, 2008: The Liddy Shriver Sarcoma Initiative and the Chordoma Foundation are co-funding a 1-year $25,500 research study, A mouse model for chordoma. This work is being funded, in part, by a very generous gift from Michael Torrey.
The study is being undertaken by Brian Harfe, PhD in the Department of Molecular Genetics and Microbiology at the University of Florida in Gainesville, Florida.
Chordomas are a very rare type of primary malignant bone tumor that affects 1 in 1,000,000 people. Traditionally, the primary treatment for this disease has been surgery. Recently, radiation therapy has been reported to be successful for the local control of the disease. However, these treatments are not optimal as the medium survival rate is just under 6 years. The rare incidence of this disease coupled with the lack of an animal model has made it difficult to develop nonsurgical therapies for this disease.
The goal of this project is to create a mouse model of chordoma. The availability of mouse models for human diseases is invaluable for developing molecular or drug-based therapies. A chordoma mouse model could quickly be provided to researchers throughout the world for use in finding a cure for this deadly disease. In this proposal I describe a genetic approach to test our hypothesis that activation of the hedgehog signaling pathway in notochordal remnants can result in the formation of chordoma. Aberrant activation of the hedgehog signaling pathway in many human tissues has been shown to lead to cancer formation. Genetics data obtained from chordomas in humans has suggested that the chromosomal region containing the hedgehog gene sonic hedgehog (Shh) is altered in these tumors. In humans, notochordal remnants residing in the spinal column have been proposed to very rarely give rise to chordomas through an unknown mechanism. Our recent data has for the first time identified notochordal remnants in the mouse model system. These cells are derived from the Shh-expressing notochord but do not express Shh themselves. Chordoma formation will be directly visualized by histology and gene expression will be assayed using antibodies specific for chordomas. The successful completion of this proposal will produce a mouse model for chordoma that will be a key reagent for developing new therapies for this deadly disease.
You can read more about the approach Prof. Harfe is taking in this study in his article,"A mouse model of chordoma," which appears in the August 2008 issue of ESUN.
Editor's Update: A progress report about this study was published in the February 2010 issue of ESUN.