Despite advances in conventional chemotherapy and radiation, complete cures for most cancer types, including sarcoma, remain elusive. The challenge is to develop highly targeted therapies that kill cancer cells but leave normal cells healthy. A big advance in cancer treatment in the past 20 years has been the discovery and application of ‘targeted therapies’. Targeted therapies are medicines that specifically act on parts of the sarcoma cells and either kill the cells or stop them growing.
If one day we can identify individuals at high risk of developing sarcomas this could lead to earlier detection and more effective treatment of these tumours. Sarcoma studies involving families have so far been limited to a lot of work in children, but the 90% of sarcomas that arise in adults have not been represented. The International Sarcoma Kindred Study (ISKS) has been set up to identify, validate and quantify genetic risk in patients with adult-onset sarcoma.
This project is based at the University of Aberdeen, but will involve collaborators from London (Institute of Cancer Research) and as far afield as Switzerland (Swiss Institute of Bioinformatics). Rhabdomyosarcomas are cancers where cells resemble dividing muscle cells. These cancers are aggressive and occur mainly in children. In this project, Dr Wackerhage and his team will study a gene called TAZ that they have found to be highly active in rhabdomyosarcomas.
During the project, the team will study various aspects of the relationship between TAZ and rhabdomyosarcoma, including:
This project will be investigating what happens to the key drugs administered to Ewing’s sarcoma patients once they have entered the body – how they are broken down and what factors are important for determining response and toxicity, to gain more information in order to improve treatment strategies. This may be particularly important for teenagers and young adults, the most commonly diagnosed group, as they may handle drugs differently to younger children. Modifying drug doses for different patient groups will allow the achievement of drug exposures which are most likely to be beneficial
Most cells of the human body have structures known as cilia, which are critical for the cell’s ability to sense its external environment. It has been suggested that there is a potential link between these structures and cancer development. In fact, 70-100% of sarcomas show loss of these primary cilia and the structures that give rise to cilia: centrioles. However, the role of cilia, and the genes associated with cilia formation in the development of sarcoma, is as yet unknown.
Pazopanib, a drug that targets a class of genes known as ‘kinases’, was recently approved for the treatment of advanced sarcoma. While some patients respond well to pazopanib, the drug does not work in all cases, meaning that some patients are exposed to the potential side effects of the treatment for little or no benefit. At present, it is challenging to predict who will respond to pazopanib, and it would be helpful to find tumour markers that enable doctors to identify the right patients to administer the drug. Furthermore, because it is unknown as to why some patients do not respond t
This project aims to identify genes which make people more susceptible to developing sarcoma by looking at a set of patients who have been diagnosed with sarcoma and another primary cancer. This is important because any genes found could be used in genetic testing for sarcoma patients and their families in the future.