Chordoma is a rare and difficult to treat bone cancer. Previous research has shown that a protein called brachyury is active in chordoma cancer cells, and when this protein is not active the cancer cells die. This project is investigating how this protein becomes active in chordoma and potential ways to switch it off.
Unravelling the epigenetic regulation of brachyury to identify new targets for the treatment of Chordoma
Chordoma is a rare cancer of the bone, occurring in 1 in 800,000 of the population with an average survival of 7 years.
Brachyury is normally found during foetal development and switches itself off around 12 weeks in the embryo. The switching off of genes as part of normal embryonic development is controlled by epigenetics. It has been recognised that abnormal regulation of genes through epigenetics is linked to cancer development. Researchers have developed inhibitor compounds that can be used as tools to learn how genes are regulated. Some of these inhibitors have been developed into drugs and tested successfully in clinical trials.
The protein brachyury is used to diagnose chordoma and laboratory research has shown that if brachyury is not active in chordoma cells, the cells die. The potential to switch off brachyury with a drug makes it attractive as a treatment option for chordoma.
This project aims to understand if brachyury is controlled at an epigenetic level by studying a number of chordoma cell lines in the laboratory. It will test a panel of more than 100 epigenetic inhibitors to see if they effect either chordoma cell growth or brachyury expression.
Inhibitors identified in this study could potentially be a future drug target for chordoma.
- Flanagan, A. M. et al. (2018) Epigenetic inactivation of oncogenic brachyury (TBXT) by H3K27 histone demethylase controls chordoma cell survival. bioRxiv. Read more: https://www.biorxiv.org/content/10.1101/432005v1
Presentations & Workshops
- Presentation given at the Pathological Society. January, 2019. Liverpool, UK.