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

Publications

Posters

  • Salawu, A. et al. Trio RhoGEF amplification a druggable target and potential biomarker in Undifferentiated Pleomorphic Sarcoma. Poster presented at the Sarcoma Research Symposium (Basic Science). September, 2016. London, UK.
  • Salawu, A. et al. One tumour, two clones: An in vitro model of intra-tumour heterogeneity. Poster presented at the European Society for Medical Oncology Congress. September, 2017. Madrid, Spain.
  • Salawu, A. et al. Trio RhoGEF is associated with tumour progression in Undifferentiated Pleomorphic Sarcoma. Poster presented at the British Sarcoma Group Conference. February, 2014. Nottingham, UK.
  • Salawu, A. et al. Identification of soft tissue sarcoma subtypes using Microarray-based Comparative Genomic Hybridisation. Poster presented at the 17th World Congress on Advances in Oncology and 15th International Symposium on Molecular Medicine. March, 2012. Crete, Greece.
  • Salawu, A., Ul-Hassan, A., Reed, M. W. R. and Sisley, K. Genetic Characteristics of Soft Tissue Sarcoma. Poster presented at the British Sarcoma Group Conference. March, 2012. Oxford, UK.

Other

  • Abdulazeez Salawu was awarded a PhD in the topic of Identiifcation of Subtype-specific Pathogenetic Abberrations in Soft Tissue Sarcoma utilising High-resolution Genomic Copy Number Analysis from the University of Sheffield. 2014.
Project status: 
completed