Funded Research

August 15, 2008: The Liddy Shriver Sarcoma Initiative is funding a 1-year $50,000 osteosarcoma research study, "PEDF: a potential therapeutic agent for osteosarcoma," at the Orthopaedics Department of St. Vincent’s Hospital in Melbourne, Australia. The funding of this grant is made possible, in part, by a generous gift from the Una O'Hagan family in loving memory of her son, Sean Keane.

Led by Professor Peter F. M. Choong, M.D. and involving Crispin R. Dass, Ph.D., this study is focused at expanding our knowledge of the potential therapeutic role PEDF (pigment epithelium-derived factor) can have against osteosarcoma (OS), and identifying the exact mechanisms that lead to its therapeutic effects. The following appears in the abstract of their grant application:

"Osteosarcoma (OS) afflicts adolescents and young adults and is fatal unless treated. Modern treatment includes limb-sparing surgery and chemotherapy with the 5-year survival rate approaching 70%. There is a need to develop strategies that combine the successes of current chemotherapy with newer agents that increase effectiveness and reduce toxicity of treatment. Despite OS’ destructive capacity, cartilage acts as a strong barrier against invasion and is only penetrated as a late local event. We were the first to link the impediment to advance of OS through the GPC [growth plate cartilage] with regulator(s) of bone maturation and the state of cartilage lacking an adequate supply of blood vessels. In analysing the molecular components of the GPC, we identified for the first time the presence of a protein called pigment epithelium-derived factor (PEDF). We have compiled a considerable amount of published data that demonstrates the effectiveness of PEDF to inhibit migration, invasion and proliferation of OS cells in vitro and these actions can be replicated in vivo. Recently, we reported that by forcibly expressing (overexpressing) PEDF in our OS model, tumor growth and metastasis were profoundly inhibited. A similar effect was also noted when we exposed developing tumor cells to recombinant PEDF protein (rPEDF). To improve the effectiveness of our strategy, we isolated shorter derivatives of the PEDF protein which contained the regions responsible for anti-angiogenic and anti-proliferative/apoptotic (programmed cell death) activity. By exposing cells in vitro and tumor in vivo, significant antitumoral activity was seen with the less expensive peptides. The main focus in our lab is to progress our PEDF research findings towards clinical evaluation and hopefully provide the first instance of successful molecular therapy for OS using endogenous biologicals."

You can read more about the approach they are taking in this study in their article, PEDF: a potential therapeutic agent for osteosarcoma, which appears in the August 2008 issue of ESUN.