Ewing’s sarcoma is a highly aggressive bone cancer that causes the bone to be destroyed. This study is looking at the processes by which Ewing’s cells disrupt normal bone biology and cause the destruction of the bone. By understanding the process by which bone is destroyed, treatments can be developed which prevent it from happening.
Analysis of osteolysis in Ewing’s Sarcoma and the effect of resorption inhibitors on tumour growth
Ewing's sarcoma is a highly aggressive bone tumour which predominantly affects children, adolescents and young adults. It is a tumour that causes extensive bone destruction and can spread rapidly. The bone destruction in Ewing’s is caused by osteoclasts, specialised bone cells which normally breakdown bone in balance with osteoblasts which build it up This study aims to look more closely at the way Ewing’s cells promote osteoclast formation which then knocks normal bone biology out of kilter, increasing bone destruction. This study may then open up a new avenue of additional treatment of Ewings and other bone sarcomas such as osteosarcoma. Sarcoma UK is funding the equipment needed for this study.
- Johansson C et al. Structural Analysis of Human KDM5B Guides Histone Demethylase Inhibitor Development. Nature Chemical Biology. 2016. (12)539-45.
- Inagaki, Y, E Hookway, K A Williams, A B Hassan, U Oppermann, Y Tanaka, and E Soilleux. Dendritic and Mast Cell Involvement in the Inflammatory Response to Primary Malignant Bone Tumours. Clinical Sarcoma Research. 2016. 6(1). BioMed Central: 1–8.
- Yusuke I et al. Sclerostin Expression in Bone Tumours and Tumour-like Lesions. Histopathology. 2016. 69(3): 470–78.
- Cheng, X., E. S. Hookway, T. Kashima, U. Oppermann, A. Galione, and N. A. Athanasou. The Role of Calcium and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) in Human Osteoclast Formation and Resorption. Calcified Tissue International. 2014. 96 (1): 73–79.
- Epigenetics in sarcoma, BTRC Meeting. 2013. Bristol.
- Epigenetic target validation in sarcoma and bone oncology, 6th International Workshop on Advances in the Molecular Pharmacology and Therapeutics of Bone and other Musculoskeletal Disease. July 2014. Oxford, UK.
- Epigenetics and metabolism in cancers of bone, Euro Bio-NMR. May 2014. Warsaw, Poland.
- The role of the lysine demethylase KDM5B and KDM6 in the Ewing sarcoma family of tumours, European Musculo-Skeletal Oncology Society conference. May 2014. Vienna, Austria.
- The effect of zoledronic acid and osteoprotegerin on tumour cell viability in Ewing sarcoma, IBMS. 2017. Brisbane, Australia.
- The Sarcoma UK funds were used to part-fund the research work of the DPhil studentship of Edward Hookway, who proved to be an exceptional student. After obtaining his DPhil at Oxford he has remained in sarcoma research field and is now working at UCL in London.
This work also led to the establishment of close collaborative ties working with Prof Adrienne Flanagan at University College London and Prof Dominque Heymann at the University of Sheffield. This has led to the investigation into the role of epigenetics in other bone sarcomas including osteosarcoma and chordoma. Initial results of these studies indicate that a similar mechanism of action of GSK-J4 is likely to be involved in these chordoma.