Accelerating drugs into clinical trials for patients with Ewing sarcoma

Ewing sarcoma is the second most common bone tumour in young people. At the time of diagnosis 25% of people present with disease in several parts of their body including the lungs and bone, so called metastatic disease. Although these patients receive a complex cocktail of drugs, surgery and radiotherapy outcomes remain one of the worst for all cancers in young people; less than 1 in 6 will survive 5-years after diagnosis. For patients with localised disease in just one part of the body, outcomes are better; up to 70% will survive beyond 5-years. However, 1 in 3 of these patients will develop widespread disease and experience the poor outcome typically associated with metastatic patients. Therefore, we urgently need new and additional treatments to improve outcomes.

In Leeds, we have used a cost-effective assay to identify drugs that kill the Ewing sarcoma cells responsible for progression and relapse. Some of these drugs treat a number of diseases, including other cancers, and in our experiments these are more effective when given in combination with ‘standard of care’ chemotherapy. In this project, we will integrate multiple experimental data and clinical experience to identify and prioritise drug combinations that target the pathways responsible for progression and relapse. We will use state-of-the-art preclinical assays to confirm the most effective tractable drug combinations are hitting their specific target(s) and refine the drug combination by systematically identifying both off-target effects and emerging resistance pathways.

The primary goal of this project is to fast-track a targeted drug combination for evaluation in clinical trials, with the aim of improving outcomes and minimising treatment associated morbidities for Ewing sarcoma patients. Once validated, the experimental pipeline could identify and fast-track targeted drugs to improve outcomes for other high-risk cancers in children and young people.