Unlike many cancers where targeted therapies have led to significant improvement in outcomes for young people, there have been few advances in the treatment for Ewing sarcoma in the last three decades.

Currently just 1 in 5 young people with the most aggressive form of this cancer survive to 5 years, and late relapse remains a significant concern. This, combined with the fact that patients currently face debilitating treatment emphasises the need to accelerate novel treatments into early phase clinical trials.

The shortage of targeted therapeutics being evaluated in Ewing sarcoma somewhat reflects the lack of knowledge of what is driving those tumour cells leading to relapse, and the variability in the behaviour of different Ewing sarcoma cells (so-called tumour heterogeneity). Even within a single tumour not all Ewing sarcoma cells are the same, which explains why relapse can arise following seemingly successful initial treatment and good responses. Improved models that faithfully represent the clinical behaviour and diversity of Ewing sarcoma are therefore essential to identify, evaluate and prioritise candidate new treatments.

In recent studies, we have used functional assays to isolate and characterise self-renewing chemotherapy resistant Ewing sarcoma cells. Through these studies we have prioritised targets that could lead to the development of more effective treatments to eradicate the most aggressive cells, which we believe are responsible for driving the tumour. The results are very promising and endorse the approach we have taken so far. However, other non-tumour cells within and adjacent to the tumour can alter how the tumour grows and responds to treatment. We aim to develop a multicellular pre-clinical model combining Ewing sarcoma and normal cells from the tumour micro-environment, to evaluate the effect of new candidates for the development of more effective treatment.

What is this project aiming to do?

This project will generate a unique preclinical tool combining Ewing sarcoma and tumour microenvironment cells for testing and prioritising different treatments. In the future we will propose this model as part of an international preclinical analysis pipeline which we hope will lead to much needed harmonization of studies to evaluate potential new treatments. Such a pipeline would enable results from different research groups to be meaningfully compared and accelerate the prioritisation of compounds for early phase clinical trials.

This project is being jointly supported by the Ewing Sarcoma Research Trust and the Bone Cancer Research Trust.

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