Euro Ewing Consortium

International Clinical Trials to Improve Survival from Ewing Sarcoma

Abstracts from young researchers at July 2016 EEC meeting, supported by Peter Pan Charity

Dr Alessandro Parra, Istituto Ortopedico Rizzoli, Italy

Analysis of CD99 SNPs as a means for predicting the Ewing Sarcoma risk

Summary of research
What are you trying to find out?
If a gene, that is highly expressed in Ewing sarcoma (CD99), is useful for the prediction of the risk that one can have of developing the pathology at a paediatric stage (under 14 years of age).

What have you found?
In the CD99 gene there are two SNPs (variants of the genic sequence) that give, if present with a special combination of the two variants, a higher risk to develop Ewing Sarcoma in paediatric patients (<14 years)

Why is this important?
With this finding it is possible to identify young people that have a higher risk to develop the EWS pathology and give them a more personalised level of attention and care to signals that can make suspicious of an onset of Ewing Sarcoma.

Florencia Cidre Aranaz, Carlos III Health Institute, Madrid, Spain

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma

Summary of research
What are you trying to find out?
In our laboratory we are currently trying to assess the role of different genes in the pathogenicity of Ewing sarcoma in order to detect good candidates for the development of potential future treatments.

What have you found?
We have found that SPRY1 is an EWS-FLI1 repressed gene and that its re-expression functionally impairs proliferation, clonogenic growth, migration and ERK/MAPK signalling in Ewing cell lines, which are features usually linked to tumorigenesis. In addition treatment of Ewing sarcoma cells with a potent FGFR inhibitor reduced proliferation, colony formation and in vivo tumor growth in a dose-dependent manner, thus mimicking SPRY1 activity in Ewing sarcoma cells. Finally, higher SPRY1 expression levels in primary Ewing sarcoma tumors are significantly associated with improved outcome in a large patient cohort.

Why is this important?
These results suggest that targeting this pathway can constitute a promising therapeutic approach for this devastating disease.

Dr Stefan Zöllner, University Hospital Munster, Germany

Small molecule inhibition of EWS-FLI1 leads to G2/M cell cycle arrest and enhanced vincristine sensitivity in Ewing sarcoma

This summary will be made available after the data has been published.

The EURO EWING Consortium is very grateful to the Peter Pan Charity for their support in enabling researchers at an early stage in their careers to present at EEC meetings.