Sarcoma UK research project
Principal Investigators: 

Dr Karen Sisley, Dr Abdulazeez Salawu, and Dr Martin Robinson

Award Amount: 
£75,790
Duration: 
3 years

This is a basic science project, finding out more about how chromosome abnormalities in the nuclei of sarcoma cells might upset the regulation of cell turnover. If they can understand more about this it might be an opening to developing new approaches to treatment. 

Sarcomas often have abnormalities in the chromosomes in tumour cell nuclei. In some forms of sarcoma, GIST for example, these chromosomal abnormalities play a major part in the development of the sarcoma and can even act as a marker to confirm the diagnosis and be a target for treatment. Imatanib was developed to treat GIST by targeting the C-kit receptor where a particular abnormality had been identified.

In other sarcomas like leiomyosarcoma the chromosomal abnormalities are more varied. Consistent patterns have not been identified. However, in an earlier study the researchers identified frequent chromosomal abnormalities in leiomyosarcomas and GIST which contain genes well known to be involved in the development of sarcomas, such as ataxia telangiectasia mutation (ATM) and retinoblastoma (RB) genes. These genes are important in regulatory mechanisms in the development of cancer, such as cell division and damage to DNA. The mutation of the ATM gene may be of particular importance as it could lead to new treatments.

Basically, people with ATMs are limited in the ability to repair DNA damage. A new class of drugs, PARP inhibitors, can knock out alternative DNA repair mechanisms. This might sound like a worse situation but in fact it means that with even fewer ways of repairing DNA, the cells might become much more susceptible to treatments such as radiotherapy.

Outputs

Presentations:

  • Trio RhoGEF amplification a druggable target and potential biomarker in Undifferentiated Pleomorphic Sarcoma. Poster presentation at Sarcoma UK Basic science research Symposium, London 2016.

Publications:

  • Establishment and molecular characterisation of seven novel soft-tissue sarcoma cell lines. A. Salawu, M. Fernando, D. Hughes, M. Reed, P. Woll, C. Greaves, C. Day, M. Alhajimohammed and K. Sisley. British Journal of Cancer 115, 1058-1068 (25 October 2016) | doi:10.1038/bjc.2016.259
Project status: 
completed