Professor Susan Burchill
University of Leeds
Sarcoma UK is investing in research leaders of the future. Our PhD programme aims to start a researcher’s career in sarcoma by funding a training fellowship which focuses on a hypothesis-driven research project.
This PhD project is investigating ways to turn off a protein called c-MYC which drives cancer progression in Ewing’s Sarcoma. The data from this research will provide important groundwork for the development of future treatment options.
Targeting MYC in Ewing’s Sarcoma
Normal cells contain a number of genes, molecules and pathways which are dormant. In Ewing’s sarcoma some cells become activated, causing the Ewing’s cells to grow and divide out of control. A protein known as c-MYC protein is an important regulator in these processes. c-MYC promotes cell growth and survival in several cancers by activating large numbers of genes and is sometimes referred to as a ‘cancer supercontroller’.
If c-MYC could be switched off, this would reverse progression and relapse of cancer in patients. At present, there are no clinically useful drugs that directly switches off c-MYC. However there is evidence that a related protein, N-MYC, which is active in neuroblastoma cancer cells, is controlled by the protein Aurora-A.
It has been shown that Aurora-A and c-MYC are expressed together in Ewing’s sarcoma cells and that inhibitors of Aurora-A can decrease c-MYC and kill these cells. This project hypothesises that Aurora-A regulates expression of c-MYC and is an attractive candidate for the development of new treatments. This project will assess the effect of known Aurora-A inhibitors to identify those that most effectively kill Ewing’s sarcoma cells.
The project will also investigate how Aurora-A regulates c-MYC protein expression and will provide tools to predict whether treatment with Aurora-A compounds is likely to be effective in Ewing’s sarcoma cells, which may be exploited to develop more personalised treatment in the future.