Osteosarcoma is the most common primary bone tumour of the skeleton, and there is unfortunately very little knowledge on the mechanisms and factors that cause normal osteoblasts, the cells that form bone, to grow abnormally and form a tumour. Very often, patients present with already established tumours making it very difficult to understand the processes underlying the early onset of tumour growth. In common with most cancers, Osteosarcoma is likely to arise through deregulation of the processes that control the normal growth, proliferation and survival of specific cells, in this case, bone-forming osteoblasts.

In general, one common therapeutic strategy is to understand the processes that lead to this deregulated state and once this is known identifying means by which this deregulation can be reversed. One means by which these processes are controlled in normal cells is via secreted factors that act as 'molecular keys' (growth factors), that activate 'molecular ignition switches' (growth factor receptors) present on the surface of cells. Activation of these receptors results in activation of specific signalling pathways within cells that control cell growth and cell survival. It is now well established that these pathways, which are tightly controlled in normal cells, are commonly perturbed in cancer cells, leading to undesired effects on the growth control of cells. Indeed, in some cases targeting of growth factor receptors has proved a highly effective treatment for cancer, the most publicised recently being the drug Herceptin, which functions to block inappropriate receptor signalling in breast cancer.

We have recently obtained preliminary evidence in a mouse model of human Osteosarcoma, that bone tumour cells present at the earliest stages of tumour formation contain alterations in one particular receptor called the Fibroblast Growth Factor Receptor (FGFR). This was subsequently validated in human Osteosarcoma samples, implicating for the first time this signalling pathway in the growth of human Osteosarcoma cells. The aim of this project is to investigate in greater detail the importance of FGFRs in the growth and survival of human Osteosarcoma cell lines, with a view to understand how these specific signalling pathways are perturbed specifically in tumour bone cells versus normal bone cells. These studies will provide essential preliminary insights into whether alterations in FGFR signalling are associated with the earliest stages of Osteosarcoma tumour growth and will define a potential novel target for therapeutic intervention.

Dr Agamemnon Grigoriadis, King’s College, London