Optimising therapy in newly diagnosed metastatic Ewing sarcoma

Ewing sarcoma is a rare cancer of the bones and soft tissue, which primarily affects those under 20 years of age.

Although chemotherapy can be effective, in 1 in 4 patients the cancer has already spread at the time of diagnosis. In this scenario, treatment is much less effective and survival rates are poor.

This study aims to discover new biological markers in the tumour to identify those patients at the highest risk of poorer outcomes and those who are likely to benefit from novel therapies.

The anticancer drug lenvatinib blocks the formation of tumour blood vessels and tumour growth, and early research indicates that adding this to standard chemotherapy may improve the treatment and survival for patients with Ewing sarcoma. An upcoming clinical trial will test this combination of lenvatinib and chemotherapy.

Our laboratory has previously identified biological signatures which predict which sarcoma patients are most likely to respond to a class of anti-cancer drugs (that include lenvatinib) which target tumour growth and blood vessels.

In this project, we will determine if these signatures can be applied to patients with Ewing sarcoma to predict lenvatinib response.

This will involve

1. Molecular analysis of biobank samples from patients with metastatic Ewing sarcoma to identify these biological signatures.
2. Assessing these signatures for clinical parameters and risk of aggressive disease and
3. Determining if these signatures can be used to predict for lenvatinib response in Ewing sarcoma patients enrolled in a clinical trial.

The overarching aim is to identify biological signatures for use in Ewing sarcoma which can help predict treatment response or risk of aggressive disease prior to starting treatment. Ultimately, our work will provide tools which allow doctors to personalise therapy, ensuring lenvatinib and other related drugs are used effectively to improve outcomes of Ewing sarcoma patients.